6 7 MHC and Presentation

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Biol 430 Question Bank MHC and Antigen Presentation

1. Describe the structures of MHC-I and MHC-II proteins.

A. Draw a schematic diagram of an MHC-I type

protein and label its peptide subunits.-------------------------------- membrane

B. he diagram to the right shows a cross-section of the MHC-I binding cleft. Add to thediagram a 1! amino acid peptide of around

showing how it would be positioned. "abel

the position of the anchor amino acids.

C. Draw a simplified diagram of an MHC-II

type protein and label its peptide subunits.-------------------------------- membrane

D. he diagram to the right shows a cross-section

of the MHC-I binding cleft. Add to the

diagram a 1! amino acid peptide of aroundshowing how it would be positioned. "abel

the position of the anchor amino acids.

#. Complete this table to show the arrangement of MHC-I$ MHC-II and MHC-III regions and geneson the chromosome.

MHC class%

"ocus% &'A

A. Although there are the same number of MHC-I and MHC-II loci$ a greater number of MHC-

II peptides can be created. (hy)

B. MHC-II loci include pseudogenes* what are these and do they contribute to the range of

peptides presented by MHC proteins)

+. Identify the meaning of each of the following designations%

Biol ,+ uestion Ban/ MHC 0 A-2resentation

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A. D34 and D35 %

B. D3A and D3B %

C. D3B1$ D3B#$ D3B+$ etc %

D. D3B161$ D3B16#$ D3B16+$ etc %

7. D3B1611$ D3B161#$ D3B161+$ etc %

8. D31$ D3#$ D3+$ etc

,. Match each of the following terms with its best e9planation.

erm

1. ::: Codominance a. MHC proteins contain more than one peptide subunit.#. ::: 2olygenicity b. A MHC protein can bind to a many different peptides.

+. ::: 2romiscuous binding c. here are se;eral genes for MHC-I and MHC-II proteins,. ::: uartenary structure d. (ithin the population there are many alleles for the MHC genes.

!. ::: 2olymorphism e. H"A genes on both homologous chromosomes are e9pressed.

!. Answer the following


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@. Consider a hypothetical allelic combination H"A-B, and H"A-C@ that presents a relati;e ris/ of

1! for a particular autoimmune disease.

A. (ill all people that ha;e the disease carry these two alleles)

B. (ill e;eryone with these two alleles get the disease)

C. (hat other factors might influence incidence of the disease)

. ou cross a homogenous C!Bl'@ >H-# b? mouse and homogenous CBA >H-#/ ? mouse$ ande9amine the H-# protein e9pression among the offspring. his diagram shows the arrangement of

MHC genes in the mouse MHC comple9.

MHC class% I II III I"ocus% A 7 D "

A. (hat H-# haplotype>s? will be carried by the 81 offspring) (ill the offspring be syngeneic)

B. (hich types of MHC will be e9pressed on the li;er cells of the offspring) (hich will be

e9pressed on dendritic cells)

=. In an in;estigation of induction of B-cell tolerance to self-antigens$ &emaee and Bur/i createdtwo transgenic mice strains. Ene recei;ed the gene for an antibody against the b protein$ the other

recei;ed this gene as well as the b gene. In the single transgenic mice$ B-cells e9pressing the anti-

b antibody were found in the bone marrow and lymph nodes$ but these B-cells were found only inthe bone marrow of double transgenic mice.

A. (hat does the e9pression F bG mean)

B. (as the haplotype of the mice recei;ing the genes H-# b or a different haplotype) 79plain.

C. If the mice did ha;e a haplotype of H-# b$ how would the results ha;e been different)


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=. As a student in an immunology laboratory class$ you ha;e been gi;en spleen cells from a mouse

immunied with the "CM ;irus. ou determine the antigen-specific functional acti;ity of these cells

with two different assays% in assay 1$ the spleen cells are incubated with macrophages that ha;e been briefly e9posed to the "CM ;irus* the production of interleu/in # >I"-#? is a positi;e response*

in assay #$ the spleen cells are incubated with "CM -infected target cells* lysis of the target cells

represents a positi;e response in this assay. he results of the assays using macrophages and targetcells of different haplotypes are presented in the table below.

Mouse strain used as

source of macrophages

0 target cells

MHC Haplotype of macrophagesand ;irus-infected target cells

3esponse of spleen cells

I"-# production by

-cells >assay 1?

"ysis of "CM-

infected cells >assay

#?

MHC-I MHC-II MHC-I

A 7 D

C+H / / / / -BA"B'c d d d d -

BA"B'c 9 B1.A d'/ d'/ d'/ d'd

A.l s / / d

B1.A >+3? b b b d -

B1.B >+3? / / -- b -

A. he acti;ity of which -cell population is detected by each assay)

B. he functional acti;ity of which MHC molecule is detected in each assay)

C. MHC molecules of which haplotypes are re


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11. 8igure >a? shows the mouse parental MHC haplotypes

and that of their offspring. he lower diagram shows an

e9perimental design where s/in is grafted from the donor mice >center column? to either inbred mice >left-hand

column? or to heterygous mice >right-hand column?.

Jame-colored mice are syngeneic.A. (hat do the designations b'b or /'/ or b'/ signify

about each mouse)

B. In which of the recipients will the s/in graft be

percei;ed as FselfG)

C. (hich of the mice will reKect the s/in grafts)

79plain why.

1#. 3eferring to the 8igure A%

A. Identify the structures labeled A - D and thecellular compartments labeled as D and 8.

B. (hat type of MHC is being loaded with

peptide)

C. In which cell types does this process occur)

D. 79plain the process that is occurring in the

compartment labeled as C


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1+. 3eferring to the figure to 8igure B%

A. Identify the structures labeled A - D and thecellular compartments labeled as D and 8.

B. (hat type of MHC is being loaded with peptide)

C. In which cell types does this process occur)

D. 79plain the process that is occurring in the

compartment labeled as 8

1@. Morrison and Braciale performed e9periments that demonstrated the presence of two antigen

processing pathways. hey used two c cell clonesthat recognied influena hemagglutin >HA$ one of the

immunogenic surface proteins of the flu ;irus?

presented either on MHC-I or MHC-II. DCs were

incubated with either infectious or inacti;ated formsof the ;irus. he inacti;ated form retained its antigenic

properties but was unable to infect host cells.

8urthermore$ the treatments included chlorothemost common treatment for malaria? which bloc/s

endocytosis$ or emetine$ which inhibits ;iral

replication. After each treatment$ the DCs were testedfor their ability to acti;ate the c cells and the results are shown in the table.

A. (hy are both cell types acti;ated by DCs treated with infectious ;irus.

B. (hich antigen processing pathway would you e9pect to not function in cells%

a. e9posed to inacti;ated ;irus) ::::::::::::::::::::::::: b. treated with emetine) ::::::::::::::::::::::::

c. treated with chloro


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1,. Liegler and nanue performed some of the /ey e9periments that demonstrated antigen

processing in DC cells. As part of the e9periments$ the DCs were treated with paraformaldehyde to

cause Ffi9ationG$ such as in ahistology procedure$ which bloc/s

all enymatic acti;ity and Floc/sG the

cellsG proteins in place. he abilityof the DCGs to acti;ate H cells that

recognie egg-white albumin

>o;albumin$ FENAG? was tested bymeasuring release of I"-# after

se;eral alternati;e treatments%

>a? DCs were fi9ed and then

e9posed to the ENA.>b? DCs were incubated with

ENA for an hour and then fi9ed.

>c? DCs were fi9ed and then

incubated with ENA peptidefragments.

In the diagram$ ENA peptides inMHC are colored red$ other peptides

are colored blue. he results are

shown in the right-hand column. >8igure is adapted from oldsby$ et al. #+. Immunology. ! th ed. 8igure =.+?

A. (hy are peptides present in the MHC proteins e;en before e9posure to ENA)

B. Does fi9ation appear to alter the ability of MHC proteins to interact with -cell receptors)

79plain.

C. (hy do the DCs fail to acti;ate the H cells in e9periment >a?)

D. (hat does e9periment C show about the ability of mature MHC proteins to e9change peptides) Do you thin/ this process is li/ely to occur in vivo)

7. 79plain how this e9periment demonstrates the need for antigen processing.


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6 7 MHC and Presentation