I M M U N O L O G Y T O D A Y

Innate and adapt ive systems m e e t in C D I b processing and presentat ion

Prigozy, T.I., Sieling, EA., Clemens, D. et al. (1997) The mannose receptor delivers lipoglycan antigens to endosomes for presentation to T cells by CDIb molecules Immunity 6, 187-197

CD1 proteins are nonpolymorphic ~2-micro- globulin-associated surface molecules

with antigen-presenting function, notably

for nonpeptide components of mycobac-

teria, including lipid mycolic acid and the

lipoglycan l ipoarabinomannan (LAM).

Prigozy and colleagues have characterized

the CDlb-mediated presentation pathway

for LAM in monocyte-derived antigen-

presenting cells (APCs) and show that

the C-type lectin mannose receptor (MR)

is responsible for uptake of LAM.

Furthermore, in common with APC-medi-

ated presentation of major histocompati-

bility complex (MHC) class II-associated

peptides, processing of LAM involves

transport to late endosomes and the MIIC

compartment, where the MR co-localizes

with CDlb. This latter event mirrors el-

ements of 'classical' antigen presentation

by MHC class II molecules. The MR dependency of LAM uptake and

presentation was confirmed by competitive

inhibition with an alternative MR ligand,

c~-mannan. Following LAM binding and in-

ternalization, MRs were most abundant

in early endosomes, but they were also

located in late endosomes, lysosomes and,

significantly, in MIICs. LAM itself could be

followed to the late endosomal compart-

ments, where immunoelectron microscopy

clearly showed it to co-localize with CDlb. The data from both LAM and MR traffick-

ing strongly suggest that LAM can be de-

livered to MIICs for uptake, and sub-

sequent presentation to T cells, by CDlb. Although previously considered to be

separate protective entities, the pathway

outlined in this paper links pattern recog-

nition of microbial structures by the innate

immune system to the induction of adap-

tive T-cell responses. Moreover, the use of

a common pathway via MIICs clearly sug-

gests a conservative evolution between

handling of antigens by the innate and ac-

quired immune repertoires.

P r e - T C R or T C R : deve lopmenta l impl icat ions

Buer, J., Aifantis, I., DiSanto, J.R, Fehling, H.J. and yon Boehmer, H. (1997) Role of different T cell receptors in the development of pre-T cellsJ. Exp. Med. 185, 1541-1548

Can differentiation of CD4-CD8-CD25 + pre-T cells with productive T-cell receptor

(TCR)~ rearrangements be mediated in the

absence of the pre-TCR? Apparently so.

Here, Buer et al. show that mature forms of

the TCR can direct CD4-CD8-CD25 + pre-T-

ceil maturation. TCR~/B-mediated develop-

ment occurs independently of TCR~ re- arrangement and selection whereas, in

common with the pre-TCR, TCRc~ selects

only cells with productive TCR~ rearrange-

ments for expansion and maturation. Two double-knockout mouse strains

were generated that lacked the pre-Ta chain and either the TCR~ chain

(pTc~-/-TCRcx - / - ) or the TCR8 chain (pTcx-/-TCRS-/-); these mutant strains

were able to produce only TCR~/8 or

TCRcx[~, respectively. Although the ab- solute number of thymocytes in both mu-

tants was reduced to 10% (pTcx-/-TCR~ -/-)

and 5% (pTc~-/-TCRcx - /-) of normal, with

the proportion of CD4+CD8 + cells down

to 58% and 4% respectively, CD4+CD8 +

thymocyte development was still possible.

However, only in the TCR~[~ ÷ mice did all

the CD4+CD8 + cells express a TCR~ chain, indicative of selection. The inefficiency of

the endogenous TCRc~[~ in driving pre-T

maturation can be largely overcome by ex-

pression of a transgenic TCRc~ early dur- ing CD4-CD8-CD25 + pre-T-cell develop-

ment in pTc~ - / - mice. Interestingly, early

expression of TCRc~ in the absence of a

pre-TCR does leave a small subset of im-

mature CD25 ÷ cells. Overall, this study indicates that the pre-

TCR has an obligatory role in maturation

of at least some pre-T cells but that the

overall process of TCR~-dependent pre-

T-cell development requires separate, but coordinated, activity from both receptors.

A t r u e pro? C l o n i n g t h e IL -16 p recursor

Baier, M., Bannert, N., Werner, A., Lang, K. and Kurth, R. (1997) Molecular cloning, sequence, expression, and processing of the interleukin 16 precursor Proc. Natl. Acad. Sci.

U. S. A. 94, 5273-5277

Interleukin 16 (IL-16) has been shown to

function as a chemoattractant factor, a

modulator of T-cell activation and an in-

hibitor of human immunodeficiency virus (HIV) replication. Inconsistencies in the

original ly publ ished IL-16 cDNA se-

quences suggested that IL-16 is synthe-

sized in the form of a larger precursor

protein (pro-IL-16), which is then

processed to the smaller bioactive form.

Baier and colleagues have identified the

transcriptional start of the IL-16 mRNA

and have cloned, sequenced and ex-

pressed the complete pro-IL-16 cDNA in

COS-7 cells. Northern blot analysis of peripheral

blood mononuclear cells (PBMCs) and the

C8166 T-cell line using a C-terminal probe

for IL-16 reveals a major 2.6 kb mRNA

transcript. The fulMength coding se-

quence of the precursor sequence was identified using 5' rapid amplification of

cDNA ends (RACE), revealing an open

reading frame (ORF) at least 1.0 kb longer

than previously reported. The predicted

pro-IL-16 protein is of 63 or 67 kDa, de- pending on which of two potential initi-

ation codons is used, although transfection

and expression in COS-7 cells yields an

apparent 80 kDa molecule. This latter dis-

crepancy mimics a tendency of IL-16-de-

rived polypeptides to migrate aberrantly on SDS/PAGE, although it is not known

whether post-translational modification of

pro-IL-16 occurs. Processing of the pro-form of IL-16 to

smaller 39 kDa and 19 kDa proteins occurs

in the presence of CD8 ÷ but not CD4 ÷ T- cell lysates. Moreover, IL-16 mRNA ex-

pression is almost exclusively limited to

lymphatic tissues. In summar3), this s tudy helps to resolve

recent conflicting observations on IL-16

and suggests that its bioactive form is an important immune regulator, synthesized

as a pro-form with subsequent processing.

U L Y 1 9 9 7 r o l . I 8 N o . 7 3 0 ~