Current Opinion in IMMuNoLmY

Vo16 - No 6 . December 1994

Editors: Frederick Alt (USA) Philippa Marrack (USA) Editorial Board

J-F Bach (France) K Eichmann (Germany) Sir G Nossal (Australia) U Storb (USA) B Benacerraf (USA) H Eisen (USA) V Nussenzweig (USA) T Tada (Japan) B Bloom (USA) T Honjo (Japan) WE Paul (USA) S Tonegawa (USA) JA Bluestone (USA) CA Janeway, Jr (USA) K Rajewsky JJ van Rood (Netherlands) J Cambier (USA) LM Lichtenstein (USA) (Germany) ES Vitetta (USA) MD Cooper (USA) P Matzinger (USA) IM Roitt (UK) J-C Weill (France) A Coutinho (France) F Melchers (Switzerland) RS Schwartz (USA) I Weissman (USA) MM Davis (USA) G Moller (Sweden) RH Schwartz (USA) R Zinkernagel (Switzerland)

JB Natvig (Norway) L Steinman (USA)

Literature Scanners Sarah Parry (coordinator), Paul Donohoe, Catherine Cunningham,

Michael May, Richard Windsor, Gillian de Romear, Tindie Kalsi

In-house Editor: Caroline Howe Production Editor: Sue Charman Managing Editor: David Weedon

Current Biology Ltd, 34-42 Cleveland Street, London WlP 5FB, UK Tel: +44 (0)71 580 8377 Fax: +44 (0)71 580 8428

1 1994 Contents 1

FEBRUARY Innate immunity

Edited by Eric Brown, John P Atkinson and Douglas T Fearon

Antigen recognition Edited by Hans-Georg Rammensee and

John Monaco

APRIL Lymphocyte development Edited by Ada Kruisbeek and

Ursula Storb Immullological techniques

Edited by Tak W Mak

AUGUST Lymphocyte activation and effector functions

Edited by Susan L Swain and Michael Reth Immunityto infkction

Edited by Peter C Doherty and Stefan KaufmaM Immun~iency

Edited by Max D Cooper and Dani P Bolognesi

OCTOBER I j DECEMBER caflcer

Edited by Drew Pardoll Transplantation

Edited by Herman Waldmann and Terry B Strom I

I Edited by Eli E Sercarz and Syamal K Datta

Current Opinion in Immunology

Current Opinion in Immunology (ISBN 1-85922-084-3/ISSN 0952-7915) is published bimonthly by Current Biology Ltd, 34-42 Cleveland Street, London Wl P SFB, UK. Each volume consists of six issues of approximately 150 pages.

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htwatwe.

Current Opinion in Immunology Aims and organization

The Current Opinion journals were developed out of the recognition that it is increasingly difficult for specialists to keep up to date with the expanding volume of information pub- lished in their subject. Current Opinion in Immunology aims to help the reader by providing in a systematic manner:

(1) the views of experts on current advances in immunol- ogy in a clear and readable form,

(2) selections annotated by experts of the most interesting papers from the great wealth of original publications, and

(3) comprehensive bibliographic listings from the major journals for the subject.

Division of the subject into sections The subject of immunology is divided into a number of ma- jor sections and each of these sections is reviewed once a year. Each issue contains two of the major sections, and these are listed on the title page (e.g. innate immunity and anti- gen recognition). Each section is reviewed by leading author- ities who are asked to write reviews and to select those pa- pers which, in their opinion, were of particular interest. The amount of space devoted to each section is related to its im- portance and the volume of original publishing in the field.

ing workers in the relevant fields on each topic that they have selected.

Reviews and reviewers Reviewers write short review articles in which they present developments in their subject, emphasizing those aspects which in their opinion are of the greatest importance. In ad- dition, they select and provide short annotations of the pa- pers that they consider of the greatest interest tiom all those published in their subject over the previous year. This selected bibliography is printed at the end of each review. Any paper chosen by a reviewer as being ‘of special interest’ or ‘of out- standing interest’ is clearly identified. The bibliographic information used as the basis of these re- views covers all the relevant literature entered into the pub- lisher’s database during a specified one-year period. (Scanning generally lags behind the date of publication of the paper by between one and three months.) In addition, reviewers com- monly add papers published later than this period as well as papers in press and, occasionally, very recent personal com- munications.

Overview The section editor writes a short overview at the beginning of the section to introduce the reviews and to draw the reader’s

Scanning the literature The Editorial Board of the journal seizct and continually up- date the list ofjournals which publish papers relevant to im- munology (the complete list is printed at the back of each is- sue). The contents pages of these primary journals are scanned by specialists in the field and every relevant paper is assigned to at least one of the sections. After suitable checking, this bibliographic information is entered into the publisher’s own database and is available to the section editors and reviewers.

Selection of topics to be reviewed Editors for each section, who are major authorities in the field, are appointed by the Editorial Board. They divide their sec- tion into a number of topics, ensuring that the subject is com- prehensively covered and all issues of current importance are

attention to any particularly interesting developments.

Bibliography of the current world literature At the back of each issue a selected bibliography is printed of papers relevant to the sections included in the issue entered into the publisher’s database in the specified one-year period. In addition, the bibliography contains every article selected by reviewers using a variety of bibliographic databases. The bibli- ography is grouped according to topics and listed alphabetically by author within each topic. Any paper chosen by a reviewer as being ‘of special interest’ or ‘of outstanding interest’ is clearly identified. The bibliography is followed by a list of the journals scanned.

Annual index In the last issue of each volume (December) the cumulative

emphasized. Section Editors commission review; from lead- indexes of subjects and authors art: provided.

Other titles published by Current Biology Ltd Chemistry and Biology Current Biology Current Opinion in Biotechnology Current Opinion in Cell Biology Current Opinion in Genetics and Development

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Other titles available in the Current Opinion series Anaesthesiology Cardiology Gastroenterology General Surgery Hematology Infectious Diseases Lipidology

Nephrology & Hypertension Neurology & Neurosurgery Obstetrics & Gynecology Oncology Ophthalmology Orthopedics

Otolaryngology & Head and Neck Surgery Pediatrics Psychiatry Rheumatolobv Surgical Infections Urology

iv

Richard J Ulevitch and Peter S Tobias

Neil R Bastian and John B Hibbs, Jr

Craig Gerard and Norma P Gerard

Ada Kruisbeek and Ursula Storb

Naomi Rosenberg and Paul W Kincade

Hergen Spits

James Hagman and Rudolf Grosschedl

Jeffrey M Leiden and Craig B Thompson

Che-Leung Law and Edward A Clark

Stephen Desiderio

Ellen V Rothenberg

Craig B Davis and Dan R Littman

Kristin A Hogquist, Stephen C Jameson and

Michael J Bevan

Peter H Krammer, Iris Behrmann,

Peter Daniel, lens Dhein and

Klaus-Michael Debatin

Tak W Mak Editorial overview: The whole is more than the sum of its parts 291

Recognition of endotoxin by cells leading to transmembrane signaling

Assembly and regulation of NADPH oxidase and nitric oxide synthase

The pro-inflammatory seven-transmembrane segment receptors of the leukocyte

Current world literature

Contents 147

Antigen recognition 147

Innate immunity 163

List of journals scanned

Volume 6 - Number 2 - April 1994

Lymphocyte development edited by Ada Kruisbeek and Ursula Storb

Editorial overview 199

B-lineage differentiation in normal and transformed cells and the microenvironment that supports it

Early stages in human and mouse T-cell development

Regulation of gene expression at early stages of B-cell differentiation

203

212

222

Transcriptional regulation of T-cell genes during T-cell development

231

Cell-cell interactions that regulate the development of B-lineage cells

238

The B cell antigen receptor in B-cell development 248

Signaling mechanisms in thymocyte selection 257

Thymocyte lineage commitment: is it instructed or stochastic? 266

The ligand for positive selection of T lymphocytes in the thymus

Regulation of apoptosis in the immune system 279

Immunological techniques edited by Tak W Mak

125

131

140

273

Continued

Eric J Jenkinson and Graham Anderson

Rae SM Yeung, Josef Penninger and

Tak W Mak

Hua Gu

Jianzhu Chen, Yoichi Shinkai,

Faith Young and Frederick W Alt

Martin F Bachmann and Thomas M Kundig

Hideto Kaneshima, Reiko Namikawa and

Joseph M McCune

Sebastian Joyce and Stanley G Nathenson

Fetal thymic organ cultures 293

T-cell development and function in gene-knockout mice 298

Gene targeting and its application to the study of B-cell development

Probing immune functions in RAG-deficient mice

308

313

In vivo versus in vitro assays for assessment of T- and B-cell function

320

Human hematolymphoid cells in SCID mice 327

Erratum: Methods to study peptides associated with MHC class I molecules

334

Current world literature

Contents

Lymphocyte development

Immunological techniques

List of journals scanned

Volume 6 - Number 3 - June 1994

335

335

349

Lymphocyte activation and effector functions

Susan L Swain and Michael Reth

Christopher JG Peaker

Anthony L DeFranco

edited by Susan 1 Swain and Michael Reth

Editorial overview: lymphocytes: the ultimate computers?

Transmembrane signalling by the B-cell antigen receptor

Signaling pathways activated by protein tyrosine phosphorylation in lymphocytes

Bartholomew M Sefton and John A Taddie

Doreen Cantrell

Tassie L Collins, Paul D Kassner,

Barbara E Bierer and Steven J Burakoff

Louis J Picker

Richard J Armitage

Role of tryosine kinases in lymphocyte activation 372

G proteins in lymphocyte signalling 380

Adhesion receptors in lymphocyte activation 385

Control of lymphocyte homing

Tumor necrosis factor receptor superfamily members and their ligands

James P Allison CD2&67 interactions in T-cell activation

355

359

364

394

407

414

Continued

vi

Norman R Kiinman

David Gray

Michael Croft

I Nicholas Crispe

Wendy L Havran and Richard Boismenu

Margaret KT Squier and J John Cohen

Graham Le Gros and Francois Erard

Anne O’Garra and Kenneth Murphy

Susan R Webb and Nicholas RJ Gascoigne

Douglas R Green and David W Scott

Peter C Doherty and Stefan HE Kaufmann

Stefan HE Kaufmann

Melanie K Spriggs

Christine A Biron

Donald E Mosier

Peter C Doherty, Sam Hou and Ralph A Tripp

Liisa K Selin and Raymond M Welsh

Anthony A Nash and NP Sunil-Chandra

Declan j McKeever and W Ivan Morrison

C Kendall Stover

Herman F Staats,

Selection in the expression of functionally distinct B-cell subsets 420

Regulation of immunological memory 425

Activation of naive, memory and effector T cells 431

CD4/CDbnegative T cells with aB antigen receptors 438

Activation and function of +$S T cells 442

Cell-mediated cytotoxic mechanisms 447

Non-cytotoxic, IL-4, IL-5, IL-l 0 producing CDB+ T cells: their activation and effector function

453

Role of cytokines in determining T-lymphocyte function 458

T-cell activation by superantigens 467

Activation-induced apoptosis in lymphocytes 476

List of journals scanned 490

Current world literature

Contents

Lymphocyte activation and effector functions

Volume 6 - Number 4 - August 1994

Immunity to infection edited by Peter C Doherty and Stefan HE Kaufmann

Editorial overview: Novel insights and new models in a time of rapid technological change

Bacterial and protozoa1 infections in genetically disrupted mice

Cytokine and cytokine receptor genes ‘captured’ by viruses

Cytokines in the generation of immune responses to, and resolution of, virus infection

Consequences of secondary or co-infections for immunity

CD8+ T-cell memory to viruses

Specificity and editing by apoptosis of virus-induced cytotoxic T lymphocytes

553

Interactions of the murine gammaherpesvirus with the immune system

560

Immunity to a parasite that transforms T lymphocytes 564

Recombinant vaccine delivery systems and encoded vaccines 568

Mucosal immunity to infection with implications for vaccine 572

491

491

515

518

526

530

539

545

Continued

Raymond J Jackson, development Mariarosaria Marinaro,

lchiro Takahashi, Hiroshi Kiyono and

Jerry R McGhee

Tomas Ganz and Defensins Robert I Lehrer

584

Jorge E Galdn Interactions of bacteria with non-phagocytic cells 590

Max D Cooper and Dani P Bolognesi

Giuseppe Pantaleo and Anthony S Fauci

Terri H Finkel and Nirmal K Banda

Sergio Romagnani and Enrico Maggi

Satoshi Tsukada, David J Rawlings and

Owen N Witte

Warren J Leonard

Jon D Laman, Eric Claassen and

Randolph J Noelle

lmmunodeficiency edited by Max D Cooper and Dani P Bolognesi

Editorial overview 597

Tracking HIV during disease progression 600

Indirect mechanisms of HIV pathogenesis: how does HIV kill T cells?

605

Thl versus Th2 responses in AIDS 616

Role of Bruton’s tyrosine kinase in immunodeficiency 623

The defective gene in X-linked severe combined immunodeficiency 631 encodes a shared interleukin receptor subunit: implications for cytokine pleiotropy and redundancy

lmmunodeficiency due to a faulty interaction between T cells and 636 B cells

List of journals scanned

Current world literature

Contents 645

Immunity to infection 645

lmmunodeficiency 675

Vol 6 - No 5 - October 1994

Patricia E Fast, Guest editorial: Efficacy trials of AIDS vaccines: how science Bonnie J Mathieson and can inform ethics

Alan M Schultz

GP Talwar Guest editorial: Immuno-contraception

644

691

698

Continued

Cancer edited by Drew Pardoll

Drew Pardoll

Maria-Ana Ghetie and Ellen S Vitetta

Joseph C Jurcic and David A Scheinberg

Suzanne Ostrand-Rosenberg

Pramod K Srivastava and Heiichiro Udono

Craig L Slingluff jr, Donald F Hunt and Victor H Engelhard

Suzanne L Topalian

Tzyy-Choou Wu

Terry 6 Strom and Herman Waldmann

Peter Nickerson, Wolfgang Steurer,

Jiirg Steiger, Xinxiao Zheng,

Alan W Steele and Terry B Strom

Anthony Dorling and Robert I Lechler

Haruhito Azuma and Nicholas L Tilney

Herman Waldmann, Stephen Cobbold and

Geoffrey Hale

Vijay K Sharma, Baogui Li,

Ashwani Khanna, Prabodh K Sehajpal and Manikkam Suthanthiran

Alan M Krensky and Carol Clayberger

Vassiliki A Boussiotis, John G Gribben,

Gordon J Freeman and Lee M Nadler

Editorial overview

Recent developments in immunotoxin therapy

Recent developments in the radioimmunotherapy of cancer

Tumor immunotherapy: the tumor cell as an antigen-presenting cell

Heat shock protein-peptide complexes in cancer immunotherapy

Direct analysis of tumor-associated peptide antigens

MHC class II restricted tumor antigens and the role of CD4+ T cells in cancer immunotherapy

Immunology of the human papilloma virus in relation to cancer

Transplantation edited by Terry B Strom and Herman Waldmann

Editorial overview

Cytokines and the Thl/ThZ paradigm in transplantation

Prospects for xenografting

Chronic graft rejection

What can be done to prevent graft versus host disease?

Which way for drug-mediated immunosuppression? 784

The induction of tolerance to alloantigens using HLA-based synthetic peptides

Blockade of the CD28 co-stimulatory pathway: a means to induce tolerance

705

707

715

722

728

733

741

746

755

757

765

770

777

791

797

List of journals scanned 810

Continued

ix

Current world literature

Jan E de Vries

Sergio Romagnani

Hans Yssel, Stephan Fasler,

Jonathan Lamb and Jan E de Vries

Jean S Marshall and John Bienenstock

Maria-Cristina Seminario and Gerald J Gleich

Thomas J Schall and Kevin B Bacon

Eli E Sercarz and Syamal K Datta

Mark J Mamula and Joe Craft

Vincent K Tuohy, Robert B Fritz and Avraham Ben-Nun

Jacques FAP Miller and Richard A Flavell

David V Serreze and Edward H Leiter

Daniel P Gold

Gary G Singer, Ana C Carrera,

Ann Marshak-Rothstein, Carlos Martinez-A and

Abul K Abbas

Ton Logtenberg

Shozo lzui

Constantin Bona and Naomi Rothfield

Contents 811

Cancer 811

Transplantation 824

Vol 6 - No 6 - December 1994

Atopic allergy and other hypersensitivities edited by Jan E de Vries

Editorial overview

Regulation of the development of type 2 T-helper cells in allergy

Induction of non-responsiveness in human allergen-specific type 2 T helper cells

The role of mast cells in inflammatory reactions of the airways, skin and intestine

The role of eosinophils in the pathogenesis of asthma

Chemokines, leukocyte trafficking, and inflammation 865

Autoimmunity edited by Eli E Sercarz and Syamal K Datta

Editorial overview: mechanisms of autoimmunization: perspective from the mid-90’s

The expression of self antigenic determinants: implications for tolerance and autoimmunity

Self-determinants in autoimmune demyelinating disease: changes in T-cell response specificty

T-cell tolerance and autoimmunity in transgenic models of central and peripheral tolerance

Genetic and pathogenic basis of autoimmune diabetes in NOD mice

TCR V gene usage in autoimmunity

Apoptosis, Fas and systemic autoimmunity: the MRL-lpr//lpr model

How unique are pathogenic anti-DNA autoantibody V regions? 921

Autoimmune hemolytic anemia 926

Autoantibodies in scleroderma and tightskin mice 931

835

838

847

853

860

875

882

887

892

900

907

913

Continued

lgal Gery and Autoimmunity in the eye and its regulation 938 J Wayne Streilein

William M Ridgway, Regulation of autoimmune response 946 Howard L Weiner and

C Garrison Fathman

List of journals scanned 958

Current world literature

Contents 959

Atopic allergy and other hypersenitivities 959

Autoimmunity 966

A complete author and subject index to volume 6 appears at the end of this issue

Continued

Abbas AK, 913 Allison JP, 414 Alt FW, 313 Anderson G, 293 Armitage RJ, 407 Atkinson JP, 73 Azuma H, 770 Bachmann MF, 320 Bacon KB, 865 Banda NK, 605 Bastian NR, 131 Behrmann I, 279 Ben-Nun A, 887 Bevan MI, 273 Bienenstock J, 853 Bierer BE, 385 Biron CA, 530 Boismenu R, 442 Bokoch GM, 91 Bolognesi DP, 597 Bona C, 931 Boussiotis VA, 797 Brown E, 73 Burakoff SJ, 385 Cantrell D, 380 Carrera AC, 913 Chen J, 313 Claassen E, 636 Clark EA, 238 Clayberger C, 791 Cobbold S, 777 Cohen JJ, 447 Collins TL, 385 Cooper MD, 597 Craft J, 882 Crispe IN, 438 Croft M, 431 Daniel P, 279 Datta SK, 875 Davis CB, 266 De Vries JE, 847 Defranco AL, 364 DeVries JE, 835 Debatin K-M, 279 Desiderio S, 248 Dhein J, 279 Doherty PC, 5 15 Doherty PC, 545 Dorling A, 765 Downey CP, 113 Engelhard VH, 13 Engelhard VH, 733 Erard F, 453 Falk K, 45 Fasler S, 847 Fast PE, 691 Fathman CC, 946 Fauci AS, 600 Fearon DT, 73 Finkel TH, 605 Flavell R, 892

Cumulative index to authors

Volume 6 - 1994

Freeman GJ, 797 Fritz Rb, 887 GaJdn JE, 590 Canz T, 584 Cascoigne NRJ, 467 Gerard C, 140 Gerard NP, 140 Cery I, 938 Ghetie M-A, 707 Gleich GJ, 860 Gold DP, 907 Gray D, 425 Green DR, 476 Gribben JG, 797 Grosschedl R, 222 Gu H, 308 Hammerling GJ, 32 Hagman J, 222 Hale G, 777 Hammer J, 52 Haufmann SHE, 515 Havran WL, 442 Hibbs JB Jr, 131 Hogquist KA, 273 Hou S, 545 Hunt DF, 733 lzui S, 926 Jackson RI, 572 Jameson SC, 273 Jenkinson EJ, 293 Joyce S, 24 Joyce S, 334 Jurcic JG, 715 Ktindig TM, 320 Kaneshima H, 327 Karjalainen K, 9 Kassner PD, 385 Kaufmann SHE, 5 18 Khanna A, 784 Kiyono H, 572 Klinman NR, 420 Knaus UG, 91 Krammer PH, 279 Krensky AM, 791 Kronenberg M, 64 Kruisbeek A, 199 Laman JO, 636 Lamb J, 847 Law C-L, 238 Le Gros G, 453 Lechler RI, 765 Lehrer RI, 584 Leiden JM, 231 Leiter EH, 900 Leonard WJ, 631 Li B, 784 Lindahl KF, 38 Littman DR, 266 Logtenberg T, 921 Maggi E, 616 Mak TW, 291

Mak TW, 298 Mamula MJ, 882 Marinaro M, 572 Marshak-Rothstein A, 913 Marshall JS, 853 Martinez-A C, 913 Mathieson BJ, 691 McCune JM, 327 McEver RP, 75 McGhee JR, 572 McKeever DJ, 564 Miller J, 57 Miller JFAP, 892 Momburg F, 32 Monaco J, 1 Morrison WI, 564 Mosier DE, 539 Murphy K, 458 Nadler LM, 797 Namikawa R, 327 Nash AA, 560 Nathenson SC, 24 Nathenson SC, 334 Neefjes JJ, 32 Nickerson P, 757 Noelle RJ, 636 O’Garra A, 458 Ostrand-Rosenberg 5, 722 Pantaleo G, 600 Pardoll D, 705 Peaker CJG, 359 Penninger J, 298 Picker LJ, 394 Rotzchke 0, 45 Rammensee H-G, 1 Rawlings DJ, 623 Reth M, 3 Reth M, 355 Ridgway WM, 946 Romagnani S, 616 Romagnani S, 838 Rosenberg N, 203 Rothenberg EV, 257 Rothfield N, 931 Sant AJ, 57 Schall TJ, 865 Scheinberg DA, 715 Schultz AM, 691 Schwartz LB, 91 Scott DW, 476 Sefton BM, 372 Sehajpal PK, 784 Selin LK, 553 Seminario M-C, 860 Sercarz EE, 875 Serreze DZ, 900 Sharma VK, 784 Shinkai Y, 313 Singer CC, 913 Sinigaglia F, 52 Slingluff CL Jr, 733

0 Current Biology Ltd ISSN 0952-7915 xi

xii

Spits H, 212 Spriggs MK, 526 Squier MKT, 447 Srivastava PK, 728 Staats HF, 572 Steele AW, 757 Steiger I, 757 Steurer W, 757 Storb U, 199 Stover CK, 568 Streilein JW, 938 Strom TB, 755 Strom TB, 757 Stroynowski I, 38 Sum-Chandra NP. 560

Suthanthiran M, 784 Swain SL, 355 Taddie IA, 372 Takahashi I, 572 Talwar GP, 698 Thelen M, 106 Thompson CB, 23 1 Tilney NL, 770 Tobias PS, 125 Topalian SL, 741 Tripp RA, 545 Tsukada S, 623 Tuohy VK, 887 Udono H, 728 Ulevitch RJ, 125

Vitetta ES, 707 Waldmann H, 755 Waldmann H, 777 Webb SR, 467 Weiner HL, 946 Weller PF, 85 Welsh RM, 553 Wirthmueller U, 106 Witte ON, 623 Wu T-C, 746 Yeung RSM, 298 Young F, 313 Yssel H, 847 Zheng X, 757

Cumulative index to subjects

Volume 6 1994

ActA, a Listeria monocytogenes protein, function, 593

Actin filaments and associated proteins in cell motility (effector

events), 117-l 20

actin monomer binding proteins, 117, 118

additional actin binding proteins, 119

adenine nucleotides, 118-l 19

capping and severing proteins, 119

spatial localization of microfilament dynamics, 119

Adenine nucleotides, role in actin dynamics, 118-l 19

Adhesion receptors in lymphocyte activation, 385-393

CD2 coreceptor, 389-390

CD4 and CD8 coreceptors, 388-389

integrin coreceptors, 385-388

AIDS

apoptosis, 608-609

mechanisms, 609-611

appearance of non-cytotoxic, ‘ThZ-like’ CD8+ cells, 455

opportunistic infections, 539-541

role of gp39 in T-helper cell activity, 639

Thl versus Th2 responses, 616-622

cytokine factors, 616

involvement of CD4+ Th subsets, 616-618

preferential replication of HIV in ThZ-like cells rather than

induction of a Thl/ThZ switch, 620-621

‘Thl/Th2 switch’ theory in HIV infection, facts and

implications, 618-620

vaccines, efficacy trials, ethics, 691-697

Allergy

and chemokines, 869-870

role of type 2 T helper cells, 838-846

Alloantigens, induction of tolerance using HLA-based synthetic

peptides, 791-796

Allografl rejection

and cytokine programs, 758-759

see also Graft rejection

Anterior chamber associated immune deviation, and prevention

of EAU, 941-942

Anticentromere antibodies in scleroderma, 932-933

Anti-DNA autoantibody(ies)

human pathogenic, 923

murine pathogenic, 921-922

V-regions, structural basis for anti-dsDNA specificity, 922-923

Anti-DNA autoimmunity, transgenic models, 923

Anti-Fc receptor autoantibodies in scleroderma, 933

Antifibrillarin antibodies in scleroderma, 933

Antigen-presenting cells

low affinity TCR binding, 9

tumor cells as, 722-727

see also Tumor cells

Antigen recognition, 1-71

antigen presentation by non-classical class I molecules, 38-44

antigens recognized by @ T cells, 64-71

autoreactivity and T-cell recognition, 42

B cell antigen receptors, 3-8

defining rules for peptide-MHC class II interaction, 52-56

MHC class I molecules, peptides associated, 13-23

methods to study, 24-31

see also Peptides, MHC-associated

MHC class II antigen processing, biology of invariant chain,

57-63

see also Invariant chain

origin, structure and motifs of naturally processed MHC class II ligands, 45-51

peptide selection by MHC-encoded TAP transporters, 32-37

T-cell receptor recognition, 9-l 2

Anti-RNA polymerase in scleroderma, 933

Antitopoisomerase I autoantibodies in scleroderma, 931-932

Apoptosis

activation-induced lymphocyte, 476-487

in immature lymphocytes, 477-478

in mature lymphocytes, 478479

mechanisms, 479482

pre-emptive death signal model, 480-481

receptor ligation signals, 479-480

in transformed lines and hybridomas, 478

two signal:death/survival model, 481-483

types, 477479

in AIDS, 608-609

mechanisms, 609-611 in B cells, 282-284

definition, 913

in EAE, 951-952

Fas and systemic autoimmunity, the MRL-lpr/lpr model,

913-920

in immature B cells, 282

lymphocyte

genetic control, 914

other genes that regulate, 914-915

and other models of autoimmunity, 918

TNF receptor/fas superfamily, 914

and tolerance to self antigens, 913-915

in mature B cells, 282-283

regulation in immune system, 279-289

in T cells, 280-282

regulation of apoptosis in thymocytes, 280-281 of virus-induced cytotoxic T lymphocytes, 553-559

Asthma

and chemokines, 869-870

pathogenesis, role of eosinophils, 860-864

see also Eosinophils

Autoantibodies in scleroderma and tightskin mice, 931-937

Autoimmune B-cell destruction in NOD mice, 903-904

Autoimmune demyelinating disease, self-determinants, 887891

see also Multiple sclerosis

Autoimmune demyelination, antigenic diversity, 887-888

Autoimmune diabetes

the H2g7 MHC haplotype as lddl in NOD mice, 90&901

mechanisms of autoimmune j3 cell destruction in NOD mice,

903-904

in NOD mice, genetic and pathogenic basis, 900-906

Autoimmune hemolytic anemia, 926-930

genetic origin of anti-erythrocyte autoantibodies, 927

0 Current Biology Ltd ISSN 0952-7915 . . .

XIII

xiv Index to subjects

nature of erythrocyte autoantigens, 926-927 role of autoreactive and regulatory T cells, 928

transgenic model, 927-928 Autoimmune response regulation, 946954

altered MHC binding, 950

antigen-induced unresponsiveness, 949-950 apoptosis in EAE, 951-952

cytokines, 950 peripheral tolerance, 950-951

superantigens, 948-949 TCR antagonism, 952

TCR peptide-induced, 947-948

Autoimmunity

amplification, mechanisms that may facilitate, 880-884

caused by Ipr and gld mutations, 915-916

effect of MHC transgenes on development, 895

in the eye, and its regulation, 938-945

mechanisms in MRL-lpr/lpr mice, 916-918 in MRL-lpr/lpr and gld/gld mice, genetic basis, 916 role of cryptic peptides, 882-883

systemic, Fas, and apoptosis, the MRL-lpr/lpr model, 913-920 and T-cell tolerance in transgenic mice, 892-899 TCR transgenes inducing, 895

TCR V gene usage, 907-912 Autoreactivity and T-cell recognition, 42

Azathioprine in immunosuppression, 786

B7-CD28 pathway

induction of antigen-specific unresponsiveness in vitro by interruption, 802-803

in vivo, 803 B7-CD28/CTLA4 family, selective deletion and over-expression of

members, 8OO-f302 B7-CD28/CTLA4 pathway, members, significance, 797-799

6 cell(s) activation, tyrosine protein kinases and phosphatases involved

in, 374

antigen receptors, 3-8

accessory transmembrane proteins, 360-361 in B-cell development, 248-256

complexes, role of protein tyrosine kinases, 251-252

cross-link with other receptors, 5-6

and cytoplasmic tyrosine protein kinases, physical

interactions between, 374-375

internalization, 3-4

and pre-El cell antigen receptor complexes, 250-251

regulation of V(D)J recombination, 248-249

signal transducing components, 374

signal transduction from, 4-5

signalling, 359-360

structure, 372

targets of slg-stimulated tyrosine phosphorylation, 252

transmembrane signalling by, 359-363

tyrosine phosphorylation, 364

variant antigen receptors, 6

apoptosis, 282-284

regulation, 283

development

6 cell antigen receptor in, 248-256 targets of slg-stimulated tyrosine phosphorylation, 252

contribution of individual antigen receptor chains to,

249-250

dissection by flow cytometry, 249

gene targeting technology, 30%312; see also Gene targeting

technology

selection during, 420421

specific defects associated with loss of protein tyrosine

kinase function, XLA and xid, 252-253

differentiation

Ab-MLV lymphoid target cells, 205

Ab-MLV model, 204-205 Ab-MLV transformants as models for Ig-gene rearrangement,

205

active v-abl protein interferes with light chaine gene

rearrangement, 206

B-lineage markers expressed by the transformants, 205

background, 203-211

early stages, regulation of gene expression, 222-230

expression of transcription factors and potential target

genes, 223-224

transformed cell models, 204-205

early, biochemical characteristics of DNA-binding proteins that

regulate transcription, 225-226

early differentiation differentiation stage specific bHLH factors, 226

Ets family transcription factors in early B cells, 224-226

other transcription factors of interest, 226-227

specific activator protein and early B cell factor, 224 early specific genes, promoter and enhancer elements,

223-224 immature, apoptosis, 282 in vivo versus in vitro assays, 320-326

evaluation of responses, 323-324

other special properties of VSV, 324 sensitivity, 324

testing of B cells, 324

lineage development cell-cell interactions regulating, 23a247 homing, 243 324

lineage differentiation, 203-211

cytokines, 207-208 adhesion molecules, 207 hormonal regulation, 207-208

microenvironment, 206-207 IL-7 and B-cell development, 206-207

malignant, regulation of apoptosis, 283-284

mature, apoptosis, 282-283

subsets functionally distinct, selection, 420-424

mature, selective and functional divergence, 421422 and T cells, immunodeficiency due to faulty interaction

between, 636-641

Bacteria, interactions with non-phagocytic cells, 590-595 bacterial entry: subverting the host cell from the outside,

SW-592 high affinity interactions between bacterial ligands and host

receptors: the ‘invasin paradigm’, 590

signaling and subsequent modulation of the host cell

cytoskeleton: the Salmonella paradigm, 591 intracellular survival and intercellular spread: subverting the

host cell from the inside, 592-593 modulation of the endocytic vacuoles, 592-593

modulation of the host-cell cytoskeleton, 593 novel microfilament-independent entry pathway, 592

Index to subjects xv

phase variation and bacterial entry: tuning into the cell

surface, 592 Bacterial and protozoa1 infections in genetically disrupted mice,

51 a525 Bactericidal/permeability-increasing protein and LBP compared,

126 Basic helix loop helix proteins

in early B-cell differentiation, 226

in T-cell development, 231-232 4-1 BB and 4-l BBL, identification in TNFR superfamily, 409-410

Bone marrow, early T-cell progenitors, 2 12-2 14

Bone marrow transplantation, future, and GVHD, 780

Brequinar sodium in immunosuppression, 788

Bruton’s tyrosine kinase

biological factors, 623-624

function, 626-627 involvement in murine immunodeficiency, 625

involvement in X-linked agammaglobulinemia, 624625

role in immunodeficiency, 624-630

subfamily, 624

C5a receptors of the leucocyte, 140-l 45

Cancer, 705-754 direct analysis of tumor-associated peptide antigens, 733-740

heat shock protein-peptide complexes in cancer

immunotherapy, 728-732 immunology of human papilloma virus, 746-754

MHC class II restricted tumor antigens and role of CD4+ T

cells in cancer immunotherapy, 741-745 recent developments in immunotoxin therapy, 707-714

recent developments in radioimmunotherapy, 715-721 tumor immunotherapy, tumor cell as antigen-presenting cell,

722-727 Candidiasis, oral, opportunistic infection in AIDS, 539

CD2 coreceptor in lymphocyte activation, 389-390

CD3 and TCR gene targeting technology, 298-299

CD4 /CD8-negative T cells with up antigen receptors, 438441

differentiation, 439

function and dysfunction, 439-440 heterogeneity, 438-439

repertoire, 439 coreceptor, in lymphocyte activation, 388-389

role in thymocyte lineage commitment, 266-272

T-cell development and function, gene targeting technology,

298-301 CD4+

activation by tumor cells, 723-724

anti-tumor, provide help and immunological memory, 741-742

in cancer immunotherapy, 741-745

conclusions and future studies, 744

demonstrating tumor-specific CD4+ immune responses in

cancer patients, 743-744

induction of tolerance, 742-743

and professional antigen-presenting cells, 742

how do they die?, 607-608 and MHC class II and I antigens in immunity to intracellular

pathogens, 521-522

subsets, APCs for, 431-433

CD8 and activation of B cells to antibody production, 454455

coreceptor, in lymphocyte activation, 388389

development and function, gene targeting technology, 298-301

role in thymocyte lineage commitment, 266272

subsets APCs for, 433

non-cytotoxic, in vitro development, which produce IL-4,

IL-5, IL-lo, 453454

CD8+

memory to viruses, 545-552

antigen persistence and/or clonal burst size, 547-548

immunological memory, 546-547

memory physiology, homeostasis, resting T cells, bystander

effects, 549-550

memory and protection, 546-547

protection and the recall response, 547

virus models, 545-546

and MHC class II and I antigens in immunity to intracellular

pathogens, 521-522

non-cytotoxic ‘ThZ-like’

appearance in AIDS, 455

are they suppressed T ceils or suppressor T cells?, 455

subset development, influence of cytokines, 460

CD10 and BP-l and B-cell lineage development, 238-240 CD19

and B-cell lineage development, 241 /CD21 complex, and B-cell antigen receptor, 360-361

CD22 and B-cell lineage development, 242 B-cell specific transmembrane protein, 360

CD23 and CD21 and B-cell lineage development, 242-243 CD27 and CD27L, identification in TNFR superfamily, 409

CD28 -B7interactions in T-cell activation, co-stimulatory ligands: the

87 family, 416-417

co-stimulatory pathway blockade to induce tolerance, 797-807

functional outcome of CD28/CTLA4 signaling, 799-800

induction of antigen-specific unresponsiveness in vitro and

in vivo by interruption, 802-803 is anergy a permanent state, 803-804

members of the B7CD28/CTLA4 pathway, significance,

797-799 selective deletion and over-expression of members of the

B7CD28/CTLA4 family, 800-802

KTLA4 signaling, functional outcome, 799-800 role in CTLA-4, 416

and T-cell activation in vitro, 414415

in vivo, 415416

CD29-B7 interactions in T-cell activation, 414419 CD30 and CD30L, identification in TNFR superfamily, 409

CD32/FcgammaRllbl, and B-cell antigen receptor, 361

CD34

and B-cell lineage development, 238

and T-cell early development, 212-214

CD38, and B-cell antigen receptor, 361

CD40

and B-cell lineage development, 241-242 and CD40L, identification in TNFR superfamily, 408

and its ligand, gp39, 637 CD44 and B-cell lineage development, 240

CD45 and B-cell antigen receptor, 361

xvi Index to subjects

and B-cell lineage development, 241

CD80 (67/88-l) family and B-cell lineage development, 242 Cell-cell interactions that regulate development of B-lineage cells, 238-247 Chemokines, 865-873

in allergy and asthma, 869-870 branches, two, three, four, or more, 865-866 in leukocyte trafficking, 866867 non-chemotactic properties, 869

Chemokine receptors and ligands, interactions between, 868-869 functional complexes, 868-869 promiscuous, 868 shared, 868 specific, 868 virally encoded, 868

Chondroitin sulfate form of invariant chain, function, Identification, 59-60 Chromatin accessibility in T-cell development, 233-234 Co-infections

consequences for immunity, 539-544 and immunity to HIV, 541-542

Co-stimulation and cytokines, and gene targeting technology in Tcell development and function, 301-302 Common variable immunodeficiency, involvement of gp39-CD40 interaction, 638-639 Contraception, immunological, 698-704

see also Immuno-contraception Corticosteroids in immunosuppression, 786 Cryptic peptides, role in autoimmunity, 882-883 Cryptic T-cell repertoire in multiple sclerosis, 888-889 CTLA-4, CD28’s enigmatic partner, 416 Cyclosporin A in immunosuppression, 786 Cytokinefs)

in autoimmune response regulation, 950 and B-cell lineage differentiation, 207-208 and co-stimulation, and gene targeting technology in T-cell development and function, 301-302 and cytokine receptor genes, implications for virus-host interactions, 527-528 and cytokine receptor genes ‘captured’ by viruses, 526-529 and cytokine receptor negative mice, in vivo function of IFN-gamma and IL-2, 532-533 in determining T-lymphocyte function, 458466 and differentiated T-helper subsets, 460461 eosinophilderived, 86 in generation of immune response to, and resolution of, virus infection, 530-538 in CVHD, engraftment and CVL, 779 in immunity to intracellular pathogens, 522-523 influence on CD8+ T-cell subset development, 460 influence on T helper subset development, 459-460 mast-cell, 94-95 non-cytotoxic, producing CD8+ T cells, activation and function, 453457 pleiotropy and redundancy in X-linked SCID, 631-635 priming of eosinophils in vivo, 87 produced by allergen-reactive CD4+ Th2 ceils, 839 production, regulation by committed, polarized Thl and Th2 populations,

co-stimulators or suppressors?, 461 programs and allograft rejection, 758-759 receptor genes ‘captured’ by viruses, 526-529

receptors induction of tyrosinase phosphorylation, 364 virally encoded, 526-527

in T-cell development, 217 and Thl/ThZ paradigm in transplantation, 757-764

cytokine programs and allograft rejection, 758-759 therapeutic implications, 761 tolerance and role of cytokines, 759-761

transgenes in transgenic mice, 894-895 virally encoded, 526 which are critical for host defense?, 541

Cytoplasmic domains, lg and CD3, and signalling, 376 Cytoplasmic signaling molecules, phosphorylation, 375-376 Cytoplasmic tyrosine protein kinases, and antigen receptors, physical interactions between, 374-375 Cytosol

degradation of antigen, role for LMPs, 35 and ER, fate of peptides, 34-35

Cytotoxic mechanisms, cell-mediated, 447452 Fas, Fas ligand and their families, 447-448 granules and granule exocytosis, 448449 granzymes, 449450 perforin, 450

Cytotoxic T lymphocytes associated antigen, role of CD28, 416 development and preservation, 555 epitopes on human melanoma, 733, 734-735 evaluation of responses, 320-323 memory, deletion of responses after infections with heterologous viruses, 557-558 precursors, memory to viruses, 547, 548-550 specificity of acute anti-viral CTL responses, 553-554 virus-induced

reactivation of memory CTL responses, 555-556 specificity and editing by apoptosis, 553-559

Defensins, 584-589 beta, sources, structures and activities, 585-586 biosynthesis, 586 classical, sources, structures and activities, 584-585 genes, and their regulation, 586-587 insect, sources, structures and activities, 586 mechanisms of action, 587 plant antimicrobial peptides, 587 synthesis, disorders, 587

Deoxyspergualin in immunosuppression, 788 Diabetes, autoimmine, in NOD mice, genetic and pathogenic basis, 900-906 Drug-mediated immunosuppression, 784-790

anti-allograft response, 794, 785 co-stimulatory signals, 785-786 mechanism(s) of action of immunosuppressants, 786-788 T-cell surface proteins, activation and signal transduction, 784-785

Effector T cells activation, 431-437 APCs for CD4+ T-cell subsets, 431-433 APCs for CD8 T-cell subsets, 433 co-stimulatory requirements of T-cell subsets, 433-434 identification, 431

Encoded vaccines and genetic immunization, 569-570

Index to subjects xvii

Endoplasmic reticulum, TAP-mediated peptide transport across,

32-35

Endotoxic shock and TNF-Rl, 523

Endotoxin recognition, 125-l 30

membrane receptors for LPS, 126-l 27

role of serum proteins, 125-l 26

transmembrane signaling mechanisms, 127-l 28

Eosinophils, 85-90

in asthma pathogenesis, 860-864

earlier findings, 860-861

mechanisms of eosinophil activation, 862

mechanisms of eosinophilia, 861-862

treatment, 862-863

cytokine production, 86

function, 87-88

in vivo, cytokine priming, 87

recruitment, 87

structure and contents, 85-86

Erratum, 334

Ethics

aspects of immuno-contraception, 702

women’s movement, 702

and efficacy trials of AIDS vaccines, 691-697

Experimental autoimmune encephalomyelitis

antigen-induced unresponsiveness, 949-950 apoptosis, 95 l-952

myelin antigens to regulate, 946947

selfdeterminants, 887-891

see also Multiple sclerosis

Experimental autoimmune uveoretinitis

immune strategies to prevent, 942

insights into initial stages, 940-941

peptide determinants involved in, 939

prevention by ACAID, 941-942

T cell receptor usage, 940

Eye autoimmunity and its regulation, 938-945

ocular specific antigens, 939

retinal antigens, 939

sequestration of ocular antigens in transgenic mice, 941

type and nature of ocular autoantigens, 939 protective mechanisms, 938-939

Fas

and fas ligand genes, TNF receptor/fas superfamily, 914

and FasL, identification in TNFR superfamily, 408-409

systemic autoimmunity, and apoptosis, the MRL-lpr/lpr model, 913-920

Fc receptor subunits and antigen receptor, interchangeability, 376

Fertility control, vaccines, 698-699

Fetal thymic organ cultures, 293-297

growth factor studies, 294

inhibitors, 295

lymphoid-stromal interactions, 294

manipulation of lymphoid compartment, 295-296

manipulation of stromat compartment, 296

peptide effects in repertoire selection, 294-295

technical considerations, 293

whole thymus lobe cultures, 293-294

FKS06 in immunosuppression, 786

Flow cytometry in dissection of B-cell development, 249

C protein linked receptors of the leucocytes, I 40-145

G proteins in lymphocyte signalting, 380-384

p21 ras function in T cells, 381-382

regulation of p21 ras in T cells, 380-381

Gammaherpesvirus, murine, interactions with immune system,

560-563

Cammaherpesvirus-68, murine, immune response to, 561-562

Gene expression, regulation at early stages of B-cell

differentiation, 222-230

Gene targeting technology, advancement, 308-309

Gene targeting technology and B-cell development, 308-312

gene replacement in B cells, 310

identification of genetic elements controlling tg-gene

rearrangement, 3 10

insights from experiments, 309-310

Gene targeting technology and T-cell development and function, 298-307

CD4 molecules, 300-301

CD8 molecules, 300

co-receptors, 299-301

co-stimulation and cytokines, 301-302

molecules involved in signal transduction and gene

transcription, 302-304

T-cell ontogeny and peripheral effector functions, 298

TCR-CD3 complex, 298-299

Generalised lymphoproliferative disease, autoimmunity caused by

Ipr and gld mutations, 913-916

genetic basis, 916 Giant cell arteritis, TCR V gene repertoires, 909

gp39-CD40 interaction, 637-639

and common variable immunodeficiency, 638-639

gp39 gene and X-linked hyper IgM syndrome, 638

Graft rejection

chronic, 770-776

lesion, 771

pathophysiology, 771-772

prevention and treatment, 772-773

risk factors, 770-771

hyperacute, 765-769

Graft versus host disease

biology, 777-778

and future of BMT, 780

host resistance, 777-778

prevention, 777-783

biology of GVHD, 777-778

building the bridges, 781

clinical issues, 779-780

consolidating of T-cell purging, 780

cytokines in GVHD, engraftment and GVL, 779

early detection of minimal residual disease and relapse, 780

graft versus leukemia effect, 779

prediction of those at risk, 781

resistance to GVH following delayed administration of T

cells after allogeneic BMT, 779

T-cell purging of marrow grafts, 779-780

T-cell subsets mediating acute GVHD, 778

T cell subsets mediating graft rejection, 778-779

why does autoimmunity occur in chronic GVHD, 779

Granules and granule exocytosis, 448

Granzymes, 449.450

GTP-binding proteins

. . . XVIII Index to subjects

and other functions of leukocytes, 101-l 02

roles of Rat and Rho in lymphocyte function, 102

small, role in leukocyte function, 98-105

Heal shock protein-peptide complexes in cancer immunotherapy,

728-732

association of antigenic peptides, 728-729

essential role of macrophages, 730

future research, 731

role in immune response, 728

as therapeutic vaccines, 730-731

Herpesvirus- infection, murine, pathogenesis, 561-562

HIV

co-infections and immunity, 541-542

-infected patients, natural killer cells, 541

infection, ‘Thl/Th2 switch’ theory, facts and implications,

618-620

pathogenesis

does HIV kill the cell it has infected?, 605-606

how do CD4+ T cells die?, 607-608

how does HIV avoid killing the cell it has infected?,

606-607

indirect mechanisms, 605-615

primary infection, immunological and virological events,

600-601

in ThZ-like cells, preferential replication, 620-621

tracking during disease progression, 600-604

advanced stage disease, 602-603

clinically latent period, 601-602

vaccine, efficacy trials, ethics, 691-697 HLA-based synthetic peptides for induction of tolerance to

altoantigens, 791-796

Hormone-dependent cancers, and fertility control vaccines, 702

hu-PBL-SCID mouse

applications, 329

characteristics, 328-329 Human chorionic gonadotropin vaccines

ethical aspects, 702

for immuno-contraception, 699-700

Human papilloma virus immunology in relation to cancer,

746-754

immune response, 746-748

cellular immune responses, 747

humoral immunity, 746-747

other host immune responses, 748

vaccine development, 748-750

other potential vaccines, 750

peptide-based vaccines, 750

prophylactic vaccines, 748-749

prospects, 749-750

therapeutic vaccines, 749

tumor vaccines, 749-750

vector-based vaccines, 749

Hybridomas

and activation-induced apoptosis, 478

T-cell, regulation of apoptosis, 282

Hyperacute rejection, xenografting, 765-769

Immune system, regulation of apoptosis, 279-289

Immuno-contraception, 698-704

application of fertility control vaccines in hormonedependent

cancers, 702

ethical aspects, 702-703

hCC vaccines, clinical trials, 699-700

political aspects, 700-701

special problems raised, 701-702

vaccines, 698-704

clinical trials, 699

preclinical safety studies, 699

women’s movement, 701

lmmunodeficiency

due to a faulty interaction between T cells and Ei cells,

636-64 1

murine, Bruton’s tyrosine kinase involvement, 625

role of Bruton’s tyrosine kinase, 624-630

tmmunoglobulin production, and mast cells, 854-855

immunoglobulin M molecules, mutant, and internalization of

BCRs, 3

immunological memory, see Memory

Immunological techniques, 291-333

Immunosuppression, drug-mediated, 784-790

see also Drug-mediated immunosuppression

Immunotherapy

cancer

heat shock protein-peptide complexes, 728-732

role of CD4+ T lymphocytes, 741-745

of tumors, 722-727

see also Drug-mediated immunosuppession

lmmunotoxin therapy, 707-714

animal models for preclinical evaluation, 709-710

nude mice, 709-710

SCID-HU mice, 710

SCID mice, 709

development of PE-based ITS, 708-709

ITS containing other plant-derived A chains or

ribosomeinactivating proteins, 707-708

monomethoxy-polyethylene glycol-coupled ITS, 708

new ITS containing less immunogenic toxic moieties, 708

new ITS with ricin A chains, 707

progress in clinical trials, 711

vascular leak syndrome, 711

vascular targeting, 71%711

Infections

experiments in KO mice, 518-521

opportunistic, consequences for immunity, 539-544

secondary, consequences for immunity, 539-544

Inflammatory bowel disease, in KO mice, local immune system

and resident intestinal flora, 523-524

Inflammatory processes, role of eosinophils, 869-870

Inflammatory reactions, role of mast cells, 853-859

Innate immunity, 73-l 45

assembly and regulation of NADPH oxidase and nitric oxide

synthase, 131-l 39

eosinophils, 85-90

mast cells, 91-97

mechanisms of leukocyte motility and chemotaxis, 113-l 24

phospholipases and protein kinases during phagocyte

activation, 106-l 12

recognition of endotoxin by cells leading to transmembrane

signaling, 125-l 30

role of small GTP-binding proteins in leukocyte function,

98-105

selectins, 75-84

tnsulindependent diabetes mellitus

Index to subjects xix

genetic and pathogenic basis in NOD mice, 900-906

loci identified, 901-902

polygenic basis, 901-902

lntegrin coreceptors, 385-388 Interferons, expression during virus infection, 531-532

Interferon-gamma, in vivo function, cytokine and cytokine

receptor negative mice, 532-533

lnterleukins, expression during virus infection, 531-532

Interleukin-2, in vivo function, cytokine and cytokine receptor

negative mice, 532-533

lnterleukin-2 receptor gamma-chain and defective gene in

X-linked SCID, 631-635

interleukin-4

in vitro development of non-cytotoxic CD8 subsets producing,

453454

producing CD8+-derived T cells in immune responses, effector

role, 455-456

Interleukin-5

in vitro development of non-cytotoxic CD8 subsets producing,

453-t54 producing CDI+derived T cells in immune responses, effector

role, 455-456

lnterleukin-7 and B-cell development, 206-207

lnterleukin-10

in vitro development of non-cytotoxic CD8 subsets producing,

453-454

producing CD8+derived T cells in immune responses, effector

role, 455-456

lnterleukin-12, expression and function in virus infections,

534-536

Intracellular pathogens, immunity to, 521

CD4+ and CD8+ T cells and MHC class II and I antigens,

521-522

cytokines, 522-523

T-lymphocytes, 521

Invariant chain

analysis of function in vivo, 60

biological activities, 58

chondroitin sulfate form, identification, 59-60

CLIP region, interaction of peptide binding site, 5859

role in antigen presentation, 59

role in trafficking MHC class II molecules, 57-58

lnvasin paradigm, 590

ISCOMS, antigen delivery systems, 579

Lamellar protrusion and leukocyte cell motility, 120

Leukemias, radioimmunotherapy, 717-719

Leukocytes

function

phagocyte NADPH oxidase, 98

role of small GTP-binding proteins, 98-105

motility, cellular functions potentially involved, 113, 114

motility and chemotaxis

actin filaments and associated proteins in cell motility

(effector events), 117-l 20

adhesion and transendothelial migration, 113-l 14

chemotaxis, 113-l 14

early membrane events (sensor and transduction functions),

114-117

lamellar protrusion, 120

mechanisms, adherence to and transmigration across

endothelium, 113, 115

membrane cytoskeletal interactions, 120

molecular motors, myosins, 120

SH3 domains and cytoskeletal regulation, 116-l 17

pro-inflammatory seven-transmembrane segment receptors,

140-l 45

trafficking, and chemokines, 866867

Liposomes as antigen delivery systems, 579

Listeria spp., intracellular parasite, 593

Liver, fetal, early T-cell progenitors, 212-214

LMPs, role in cytosolic degradation of antigen, 35

LPS-binding protein and BPI compared, 126

Lymphadenopathy, autoimmunity, Ipr and gld mutations, 915-918

Lymphocyte(s)

activation

adhesion receptors, 385-393

and effector functions, 355-487

role of tyrosine kinases, 372-379

apoptosis, see Apoptosis, lymphocyte

development, 189-289

extravasation, molecular regulation, 39UOO

function, role of Rat and Rho GTP-binding proteins, 102

homing

control, 394-406

multistep model, 395-396

specificities, microenvironmental control, 401-402

immature, activation-induced apoptosis, 477478

retention in tissue, molecular regulation, 400

signaling pathways activated by tyrosine phosphorylation,

364-371

signalling, C proteins, 380-384

Lymphocytic choriomeningitis virus to assess T-cell function,

320-323

Lymphomas, radioimmunotherapy, 717-719

Lymphoproliferative disease models, apoptosis, Fas and systemic

autoimmunity, 913-920

Mass spectrometric method of MHC-associated peptide study,

26-27

Mast cells, 91-97

activation, clinical indicator, 94

cytokine production, 94-95, 853-854

Fc gamma receptors, function, 854

and immunoglobulin production, 854-855

in inflammatory reactions, 853-859

mediator release, regulation, 856857

nerves and neuropeptides, 855-856

neutral proteases, 91-94

function, 93-94

heterogeneity, 91-92 human, 92

molecular biology, 93

mouse, 91-92

population regulation, 855

predominant granule mediators, 91-92

Melanin protein-induced uveitis, 939-940

Melanoma, cytotoxic T lymphocyte epitopes, 733, 734-735

Memory

differentiation to memory B cells, 425426

is there a separate lineage of memory B cells, 426

long-term maintenance, 4271128

physiology, homeostasis, resting T cells, bystander effects,

549-550

xx Index to subjects

regulation, 425-430

towards a definition of memory T cells, 426

Memory B cells

differentiation, 425426

is there a separate lineage, 426

Memory T cells

activation, 431437

APCs for CD4+ T-cell subsets, 431-433

APCs for CD8 T-cell subsets, 433

co-stimulatory requirements of T-cell subsets, 433-434

identification, 431

migration, 426427

towards a definition, 426

MHC-associated peptides, 13-23, 32-37, 47

complexity and abundance of ‘naturally processed’, 13

identification of peptides that comprise class I restricted

epitopes, 18-l 9

for indurtion of tolerance to alloantigens

class I, 791-793

class II, 793-794

naturally processed, implications for antigen processing on the

basis of sequences, I, 18

role in positive selection of T lymphocytes in thymus, 274-275

structural basis, 14-l 8

peptide length and orientation, 14

side-chain selectivity and binding pockets, 14-l 8

study methods, 24-31

of allele-specific anchors, dominant and auxillary, pool

sequencing method, 25

empirical estimation, 25-26

in vitro peptide-binding assay, 27-28

mass spectrometric method, 26-27

radiochemical method, 24-25

sensitivity of CTLs, 28

MHC class I molecules, structure of peptides associated with,

13-23

MHC class lb molecules, bind peptides, 39-40

MHC class lb proteins, characteristics, 40

MHC class II antigen processing

biology of invariant chain, 57-63

see also Invariant chain

MHC class II binding peptides, 39-40

approaches to analysis, 52-53

naturally processed peptides, 52-53

phage display library, 53

substitution analysis, 52

defining rules, 52-56

role of disease-associated polymorphic residues, 54-55

sequence motifs, 53-54

allele-specific versus promiscuous binding, 53

anchor residues, 53

negative influences of particular amino acid side chains,

53-54

MHC class II ligands, sequences, 46

MHC class II proteins-peptide interaction, defining rules, 52-56

MHC-encoded TAP transporters, and peptide selection, 32-37

MHC natural class II ligands

origin, 45-46

promiscuous ligands, 4748

putative processing motif, 4849

structure, 46

MHC natural class II peptide motifs, 47

MHC, non-classical class I molecules

antigen presentation, 38-44

classical versus non-classical, is there a difference?, 39

evolution, 38

functions, 42

generalized antigen presentation: Qa-2, 41

mouse and human class lb genes, 38-39

specialized antigen presentation: M3, 40-41

tissue distribution, 39

Microspheres as mucosal antigen delivery vehicle, 578

Mizoribine in immunosuppression, 788

Monoclonal antibody therapy, physical characteristics limiting,

715-716

MRL-lpr/lpr and gld disease, immunologic abnormalities,

915-916

MRL-lpr/lpr and gld/gld mice, autoimmunity, genetic basis, 916

MRL-lpr/lpr mice, autoimmunity, mechanisms, 916-918

MRL-lpr/lpr model

apoptosis, Fas and systemic autoimminity, 913-920

autoimmunity caused by Ipr and gld mutations, 915-916

Mucosal antigen delivery systems, alternative, characterization of

immune responses with, 579-581

Mucosal immune system, organization, 572-573

Mucosal immunity, animal models, 573-574

Mucosal immunity to infection with implications for vaccine

development, 572-583

Mucosal vaccine strategies, 574-581

Multiple sclerosis

antigenic diversity in autoimmune demyelination, 887888

determinant spreading and cryptic T-cell repertoire, 888-889

immunodominant peptide determinants, 888

myelin protein determinants, 887-891

‘self’-exposure during remyelination, 889

TCR V gene usage and response to myelin basic protein,

907-908

Muscular dystrophy, TCR V gene repertoires, 910

Myasthenia gravis, TCR V gene repertoires, 909

Mycobacterium avium complex infection, opportunistic infection

in AIDS, 540

Myelin antigens to regulate EAE, 946-947

Myelin-associated glycoprotein (MAC) and multiple sclerosis, 888

Myelin basic protein

in asthma, 860

in multiple sclerosis, 887, 889

TCR V gene usage and response to, 907-908

Myelin oligodendrocyte glycoprotein (MOG) and multiple

sclerosis, 888

Myelin proteolipid protein and multiple sclerosis, 887, 888

Myosins, role in leukocyte motility, 120

NADPH oxidase

assembly, 132

background, 131-132

non-phagocyte, 133-l 34

regulation, 132-l 33

regulation by Rat, 98-99

role in phagocytic leukocytes, 98

Naive T cells

activation, 431-437

APCs for CD4+ T-cell subsets, 431-433

AF’Cs for CD8 T-cell subsets, 433

co-stimulatory requirements of T-cell subsets, 433434

Index to subjects xxi

identification, 431

Natural killer cells

in HIV-infected patients, 541

and T cells, relationship between, 216

Nerve growth factor receptor family in B-cell lineage

development, 241-242

Nerves, neuropeptides, and mast cells, 855-856

Nitric oxide and superoxide biosynthetic pathways, functions and

interactions, 135

Nitric oxide synthase

background, 131-l 32

immune/inflammatory, assembly, 134

isoforms

feedback inhbition by NO, 134

regulation, 134

Non-obese diabetic mice, autoimmune diabetes, genetic and

pathogenic basis, 900-906

see also Autoimmune diabetes

Ocular antigens, sequestration, in transgenic mice, 941

Ocular autoantigens, type and nature, 939

Ocular immunosuppressive microenvironment, 941

Ocular specific antigens, 939

Open reading frames, viral, encoding cytokines or cytokine

receptor genes, 526 OX40 and OX4OL, identification in TNFR superfamily, 410

p2 1 ras

function in T cells, 381-382

regulation in T cells, 380-381

Peptidefs)

-binding assay, class I MHC molecules, 27-28

cryptic, role in autoimmunity, 882-883

determinants

do different APCs display different determinants, 884-885

immunodominant, in multiple sclerosis, 888

involved in EAU, 939

role of invariant chain, 884

fate in cytosol and ER, 34-35

naturally occurring, comprehensive listing, 15-l 7

role in positive selection of T lymphocytes in thymus, 275

selection in antigen presentation, three levels, 35

selection by MHC-encoded TAP transporters, 32-37

indirect evidence for peptide translocation by TAP, 32-33

TAP1 and TAP2 are ABC transporters, 32

TAP independent antigen presentation, 33

self-reactive T-cells, fate, deletion, anergy or suppression,

893-894

tested for binding to H-2M3, 41

translocation, microsomal systems for, 33

vaccination of allergic patients, 849850

see also MHC

Perforin, role in cytolysis, 450

Peripheral tolerance and autoimmune response, 950-951

Phagocyte activation, role of phospholipases and protein kinases,

106-112

Phagocytic leukocytes, function, role of small CTP-binding

proteins, 98-l 05

Phosphoinositide signaling pathway of B and T cells, 366-367

Phospholipases, A2, C, D, during phagocyte activation, 106-l 07

Pneumocystis carinii infection, opportunistic infection in AIDS,

540-541

Polymorphic residues, disease-associated, and MHC class II

peptide binding, 54-55

Pool sequencing analysis of MHC class II ligands, 47, 4849

Pool sequencing method of MHC-associated peptide study, 25

Proteasome subunits LMP2 and LMP7, role in cytosolic

degradation, 35

Protein kinases, role in phagocyte activation, 107-l 09

Protein tyrosine kinases

implicated in signaling through B cell receptor complexes,

251-252

and inhibition of BCRs, 3

loss of function, specific B cell developmental defects

associated with, XLA and xid, 252-253

Protozoa1 and bacterial infections in genetically disrupted mice,

518-52.5

Psoriasis, TCR V gene repertoires, 910

Kac CTP binding protein

action, post-translational modifications, 99-100

function is regulated by interactions with [RholGDI, 100

and NADPH oxidase regulation, 98-99

and oxidant production in other immune cells, 100-l 01

role in leukocyte function, 98-l 05

translocates to plasma membrane during phagocyte activation,

99

Radiochemical method of MHC-associated peptide study, 24-25

Radioimmunotherapy of cancer, 715-721

choice of radioisotope, 716

future directions and conclusions, 719-720

hematologic malignancies, 717-719

obstacles to monoclonal antibody therapy and potential

solutions, 715-716

solid tumors, 716-717

RAG-deficient mice, probing immune functions, 313-319

analyses of T-cell differentiation, 314-315

analysis of B-cell development, 315-316

blastocyst complementation, 316-317

Rapamycin in immunosuppression, 786-787

Ras pathway of B and T cells, 367

Recombinant vaccine delivery systems, 568569

Rejection, graft

acute, xenografts, 765-767

delayed vascular, and accommodation, 767

see also Graft rejection

Remyelination in multiple sclerosis, ‘self’-exposure during, 889

Retinal antigens, 939

Rheumatoid arthritis, TCR V gene usage, are superantigens

involved, 908-909

Khodopsin, 140

Ricketssia spp., intracellular spread, 593

RS-61443 in immunosuppression, 787-788

Salmonella entry into mammalian cells, 591-592

Salmonella paradigm, 591-592

Sarcoidosis, TCR V gene repertoires, 909

SCID mice

engraftment with human hematopoietic cells, 329

prospects, 329 human hematolymphoid cells, hu-PBL-SCID mouse, 327-333

applications, 329

characteristics, 328329

SCID-hu mouse

xxii Index to subjects

applications, 328

biological construction, 327-328

Scleroderma, autoantibodies, 931-933

anti-Fc receptor autoantibodies, 933

anti-RNA polymerase, 933

anticentromere antibodies, 932-933

antifibrillarin antibodies, 933

antitopoisomerase I, 931-932

Secondary infections, consequences for immunity, 539-544

Selectin-ligand recognition, 75-78

characteristics of E-, L-, P-selectins, 75-80

Selectin mediated cell signaling, 78

Selectins, 75-84

expression, regulation, 78-79

in vivo functions, 79-80 Self antigenic determinants, expression, 882-886

do different APCs display different peptide determinants,

884-885 role of invariant chain in specific peptide presentation, 884

unconventional routes of antigen presentation may enhance

immunogenicity, 884 Self-determinants in autoimmune demyelinating disease, changes in T-cell response specificity, 887-891

Serine/threonine kinases, role in phagocyte activation, 107-l 08

Seven-transmembrane segment receptors of the leucocyte,

proinflammatory, 140-l 45

functional features, 142-l 43

structural features, 140-l 42 Severe combined immunodeficiency

defective gene, IL-2 receptor gamma-chain, 631-632 other cytokines also use gammac, 632-634

X-linked

defective gene encodes a shared interleukin receptor subunit, implications for cytokine pleiotropy and

redundancy, 631-635

four-helix bundle proteins and dimerization of receptor

chains, 634 see also SCID mice

Shigella spp., intracellular spread, 593

Signal transducing components of T- and B-cell antigen receptors,

374 Signal transduction and gene transcription, and T-cell

development and function, 302-304

Signaling, cytoplasmic domains, Ig and CD3, 376

Signaling pathways activated by tyrosine phosphorylation in

lymphocytes, 364-371

Stem cell factor and T-cell early development, 218

Superantigens

and autoimmune regulation, 948-949

interaction with class II antigens, 469-470

structure, 467469

T-cell activation by, 467475

tolerance, 472

T-cell activation in response, 470-472

T-cell responses to, in vivo consequences, 472

TCR recognition with class II antigens, 470 Superoxide and nitric oxide biosynthetic pathways, functions and

interactions, 135

Systemic lupus erythematosus, autoimmunity, 918

T cell(s)

activation

by superantigens, 467-475

CD28-B7 interactions, 414-419

in vitro, and CD28, 414-415

in vivo, and CD28, 415-416

naive, and Thl/ThZ paradigm, 757-758

in response to superantigens, 470-472

tolerance to superantigens, 472

tyrosine protein kinases and phosphatases involved in,

372-374

antigen receptors

and cytoplasmic tyrosine protein kinases, physical interactions between, 374-375

and Fc receptor subunits, interchangeability, 376

signal transducing components, 374

structure, 372

tyrosine phosphorylation, 364

apoptosis, 280-282

see atso Apoptosis

and B cells, immunodeficiency due to faulty interaction

between, 636641 contribution of thymic stromal cells, 273-274

cytokines, role, 458-466 dependent B-cell activation, 636-637

87 family and its co-receptors, CD28/CTLA-4, 637

CD40 and its ligand, gp39, 637

development and activation, transcription factors invo!ved in regulating

gene expression during, 232

bHLH proteins, 231-232

chromatin accessibility, 233-234 cytokines, role, 217

early, role of TCR beta-chains, 215-216

Ets transcription factors, 234-235 and function in gene-knockout mice, 298-307; see also

Gene targeting technology

general transcription factors, 234 HMG proteins, 233-234 homeotic genes, 232-233

human and mouse, early stages, 212-221

lineage commitment, 231-233

NF-kappaB/rel transcription factors, 234 transcriptional activators and repressors, 234-235

transcriptional regulation of T-cell genes during, 231-237

zinc finger transcription factors, 233

early precursor populations in thymus, 214-215

evaluation of CTL responses, in vivo versus in vitro assays,

320-323

knockout mice, 323

primary, 321

secondary, or CTL memory, 321-323

sensitivity, 323

evaluation of responses of T helper cells, in vivo versus in vitro

assays, 323-324

other special properties of VSV, 324

sensitivity, 324

testing, 324

gamma delta

activation and function, 442446 antigen recognition by, 443-444

antigens recognized by, 64-71

those reported, 66

Index to subjects xxiii

development and function, role of MHC, 443

functional, development, 442-443

invariant epithelial, function for, 444

mouse, populations, 64

in response to infections, 65-66

in immunity to intracellular pathogens, 521

immunity to a parasite that transforms, 564-567

see also Theileria parva

in vivo versus in vitro assays, 320-326

and NK cells, relationship between, 216

p21 ras function, 381-382

p21 ras regulation, 380-381

peripheral

malignant, regulation of apoptosis in hybridomas, 282

regulation of apoptosis, 281-282

positive selection in thymus, 273-278

model, 275-276

peptides, role, and approaches, 274-275

progenitors, early, characterization in bone marrow and fetal

liver, 212-214

purging, consolidating, 780

receptor antagonism in autoimmune response, 952 receptor p-chains, role in early T-cell development, 215-216

receptor peptide-induced regulation of autoimmune response,

947-948

receptor recognition, 9-l 2 crosslinking versus conformational change of the TCR,

alternatives for T-cell triggering, 1 O-l 1 low affinity is sufficient, 9-l 0 of superantigen with class II antigens, 470

receptor usage in autoimmune uveitis, 940

receptor V gene repertoires in autoimmune diseases, 909-910

receptor V gene usage in autoimmunity, 907-912 in multiple sclerosis and response to myelin basic protein,

907-908 in rheumatoid arthritis, are superantigens involved, 908909

receptors, gamma delta, antigen recognition by, and alphabeta

paradigm, 66-67 recognition, and autoreactivity, 42

responses to superantigens, in vivo consequences, 472

subsets co-stimulatory requirements, 433-434

mediating acute CVHD, 778

mediating graft rejection, 778-779

tolerance and autoimmunity in transgenic mice, 892-899 helper cells

and cytokines in transplantation, 757-764

phenotype development, analysis, are all starting populations

naive?, 459

subsets

cross-regulation between 1 and 2, 462

differentiated, and cytokine pattern, 460-461

Thl versus Th2 responses in AIDS, 616-622

Thl/ThZ paradigm and cytokines in transplantation, 757-764

cytokine programs and allograft rejection, 758-759

therapeutic implications, 761

tolerance and role of cytokines, 759-761

‘Thl/Th2 switch’ theory in HIV infection, facts and implications, 618-620

type 2 (Th2), allergen specific, 838-846 allergen challenge causes activation and recruitment in

target organs, 840

allergens preferentially expand Th cells showing a ThZ-like

profile, 838

anergic Th2 clones fail to provide B-cell help, 848

anergy induction, effects on expression of surface molecules

and signal transduction, 848849

antigen-presenting cells and T-cell repertoire, 840-841

central role in pathogenesis of allergy, 838

expressing membrane CD30, present in circulation of

allergic patients, 840

induction of non-responsiveness, in vitro and in vivo

models, 847-852

mechanisms involved in regulation of development,

840-842

microenvironmental cytokines, 841-842

microenvironmental hormones, 841

peptide vaccination of allergic patients, 849-850

possible genetic alterations favoring responses in atopic

subjects, 842-843

specific immunotherapy can change cytokine profile, 840 ThZ-like cells accumulate in target organs of allergic

patients, 839-840 TAP

independent antigen presentation, 33

novel transport assay, 33-34

size selection, 34 TAP1 and TAP2 are ABC transporters, 32

transporters, MHC-encoded, and peptide selection, 32-37 Theileria parva

immune responses of cattle to, 564-565

immunity to, 564-567 vaccine impact, 566

sporozoite neutralization, 565-566

T lymphocyte responses, effector mechanisms in vivo, 565 Thymic stromal cells, and positive selection of T lymphocytes,

273-274

Thymocytefs) cortical, unique physiological environment for activation,

257-259 early developmental transition inudced by TCRfi gene

product, 258-259 high sensitivity to TCR ligands through novel balance of

signals, 257-258

possible control of negative selectability via Bcl-2 and Fas,

259

lineage commitment, 266-272

appearance of intermediate thymocyte populations (CD4+CD8lo or CD4loCD8+) in mice defective for MHC

expression, 269

co-receptor expression and interaction with p56lck are not

essential, 268-269

co-receptor regulation of thymocyte progression to maturity, 270

is there room for instructional signaling?, 270

models of differentiation of SP thymocytes, 266-268 rescue of mismatched intermediate thymocytes by ectopic

expression of co-receptor, 270 why are co-receptors necesssary?, 271

regulation of apoptosis, 280-281 selection, signalling mechanisms, 257-265

accessory ligand requirements for positive and negative

selection, 260

xxiv Index to subjects

CD4/CD8 signaling in positive selection, 260-261

co-receptor signaling mediators in selection, 260-261

implications for self-definition, 260

ligands and accessory cells for positive and negative

selection, 259 lineage-independent triggering, lineage-dependent

maturation?, 261 positive selection is biphasic, 261

TCR ligands, 259 Thymus

early T-cell precursor populations, 214-215

positive selection of T lymphocytes, 273-278

model, 275-276

see also Fetal thymic organ Tightskin scleroderma-like syndrome, autoimmunity associated

with, 934

Tolerance

and expression of self antigenic deternminants, 882-886

induction, blockade of CD28 co-stimulatory pathway, 797-807

induction to alloantigens using HLA-based synthetic peptides,

791-796 T-cell, and autoimmunity in transgenic mice, 892-899

Toxoplasmosis, opportunistic infection in AIDS, 541

Transcription factors, role in tyrosine phosphorylation, 367 Transforming growth factor-beta, expression and function in virus

infections, 533

Transgenic mice

model of autoimmune hemolytic anemia, 927-928

models of anti-DNA autoimmunity, 923 sequestration of ocular antigens, 941

T-cell tolerance and autoimmunity, 892-899 cytokine transgenes, 894-895

effect of MHC transgenes on development of autoimmunity,

895 fate of peripheral self-reactive T cells, deletion, anergy or

suppression, 893-894 intrathymic selection, 892-893 TCR transgenes inducing autoimmunity, 895

Transmembrane signaling mechanisms and endotoxin recognition,

127-l 28

Transplantation, 755-807

blockade of CD28 co-stimulatory pathway to induce tolerance,

797-807 chronic graft rejection, 770-776

cytokines and Thl/ThZ paradigm, 757-764

induction of tolerance to alloantigens using HLA-based

synthetic peptides, 791-796

prospects for xenografting, 765-769 what can be done to prevent graft versus host disease,

777-783

which way for drug-mediated immunosuppression, 784-790

see also Graft rejection Transporter associated with antigen processing, see TAP

Trials, AIDS vaccines, efficacy, and ethics, 691-697 Tuberculosis, opportunistic infection in AIDS, 540

Tumor-associated peptide antigens, 733-740

approaches for identification of peptide epitopes, 733-734

identification of T cell defined epitopes expressed on

melanoma cells, 734-735 identification of T cell defined epitopes expressed on other

tumor cells, 735-736 Tumor cells as APCs

activation of CD4+ and CD8+ T cells by tumor cells

transfected with co-stimulatory molecules, 724

activation of CD4+ T-helper lymphocytes by tumor cells

transfected with MHC class II genes, 723

activation of effector cells by tumor cells secreting cytokines,

722-723

host-derived APCs can present tumor peptides, 725

stimulation of tumor immunity by re-expression of lost MHC

class I molecules, 724

where does antigen presentation occur, 724-725

Tumor immunotherapy, 722-727

Tumor necrosis factor-R1 and endotoxic shock, 523

Tumor necrosis factor receptor superfamily

4-1 BB and 4-1 BBL, 409-410

CD27 and CD27L, 409

CD30 and CD30L, 409

CD40 and CD40L, 408

Fas and FasL, 408409, 914

members and their ligands, 407-413

OX40 and OX4OL, 410

Tyrosine kinases

role in lymphocyte activation, 372-379

role in phagocyte activation, 108-l 09

Tyrosine phosphatases

involved in B-cell activation, 374 involved in T-cell activation, 372-374

Tyrosine phosphorylation

in lymphocytes, signaling pathways activated by, 364-371

receptor-induced B-cell and T-cell antigen receptors, 365

choice of targets, 365-366

cytokine receptors, 364

nature of targets, 364-366 signaling events regulated by targets, 366-368

direct activation of transcription factors, 367

phosphoinositide signaling pathway, 366-367

Ras pathway, 367 regulation of intracellular trafficking and/or the cytoskeleton,

367-368

Tyrosine protein kinases cytoplasmic, and antigen receptors, physical interactions

between, 374-375 involved in B-cell activation, 374

involved in T-cell activation, 372-374

Dveitis, melanin-protein-induced, 939-940

V-regions, pathogenic DNA autoantibody, unique characteristics,

921-925

Vaccine delivery system, recombinant, 568-569

live recombinant bacterial vaccine vehicles, 568569

live recombinant viral vaccine vehicles, 569

Vaccine development

animal models for mucosal immunity, 573-574

DNA vaccines, 578

in HPV-associated neoplasms, 748-750

implications of mucosal immunity to infection, 572-583

ISCOMS, 579

liposomes, 579

live vectors, 575-578 attenuated recombinant bacteria, 575-577

attenuated recombinant viruses, 577-578

index to subjects xxv

microspheres, 578 resolution of, 530-538 mucosal vaccine strategies, 574-581

novel antigen delivery systems, 579

organization of mucosal immune system, 572-573

effector tissues, 573

inductive tissues, 572-573

virus-like particles, 578

Vaccine to Theileria parva, 566

Vaccines, encoded, and genetic immunization, 569-570

Vaccines for control of fertility, 698699

clinical trials, 699

Virus-like particles as antigen delivery system, 578

Vi ruses

CD8+ T-cell memory, 545-552

cytokine and cytokine receptor genes ‘captured by, 526529

VLA-4 tCD49d/CD29) and B-cell lineage development, 240-241

see also Immune-contraception

Vascular leak syndrome and immunotoxins, 711 Vesicular stomatitis virus to assess B-cell and T-cell function,

323-324 Viral infection

acute

X-linked agammaglobulinemia

Bruton’s tyrosine kinase involvement, 624625

and XID deficiencies, comparison, 625

X-linked hyper IgM syndrome and mutations in the gp39 gene, 638

editing and resolution, 554-555 impaired memory T-cell responses during, 556

X-linked severe combined immunodeficiency, defective gene

encodes a shared interleukin receptor subunit, implications for

cytokine pleiotropy and redundancy, 631-635

Xenografting prospects, 765-769

cellular responses, 767

delayed vascular rejection and accommodation, 767

hyperacute rejection, 765-767

cytokkws in generation of immune responses to, and Yersinia entry into non-phagocytic cells, 598-591