Major Histocompatability Complex: Structure and Function

Question 1

Passive immunization

Answer 1

Transferring B cells (serum antibodies) from a previously infected host to a non-infected host to transfer protection from infection to the non infected host

Question 2

Why is passive immunization in humans expensive?

Answer 2

Gamma-globulin (IgG) injection for HIV patients has half life of about 30 days

Question 3

Will the transfer of T cells protect a new host? Why or why not?

Answer 3

Only if the two hosts are genetically identical
T-cells always recognize foreign antigen in the context of self
New strain has different “non-self” MHC molecules presenting the antigen

Question 4

MHC restriction

Answer 4

T-Cell receptors are specific for LCMV antigen, but are restricted by self-MHC, so they don’t protect allogeneic host

Question 5

What happens when tumors are transplanted from one strain of mice into same inbred and different inbred strains

Answer 5

Tumors flourished and killed syngeneic mice

Tumors were rejected when implanted into allogeneic mice

Question 6

Tumor rejection genes are ________

Answer 6

codominant

Question 7

Gene structure of MHC

Answer 7

Over 200 genes are encoded within the MHC which spans 7 million base pairs on chromosome 6

Question 8

HLA

Answer 8

Human leukocyte angtigen (Gene of class I MHC)

Question 9

Class I: three classical gene products

Answer 9

HLA-A, -B, -C (“heavy chains”)

Question 10

Class II: Six classical gene products, heterodimers

Answer 10

HLA-DR, -DQ, - DP, - (α and β chains)

Question 11

How can T cells see the widest possible variety of antigens?

Answer 11

Polygenic (3 genes)
Codominant (Each gene is co-dominant)
Polymorphic (numerous identified alleles in the human population at each locus)

Question 12

What type of screening is done before bone marrow transplantation?

Answer 12

Tissue typing for MHC class I and class II
1:4 chance of another sibling matching for all 10 products assuming no recombination between loci

Question 13

Human Class I MHC molecules (6)

Answer 13

1) Three classical class I MHC gene products: HLA-A, HLA-B, HLA-C
2) Highly polymorphic
3) Class I MHC molecules are expressed on all nucleated cells
4) Class I MHC molecules play a major role in allograft rejection
5) Class I MHC molecules present peptide antigens to CD8 T Cells
6) Class I heavy chain forms heterodimers with a light chain, β2 microglobulin

Question 14

Human Class II MHC Molecules (7)

Answer 14

1) Three class II MHC gene products: HLA-DR, HLA-DQ, HLA-DP
2) Highly polymorphic
3) Class II MHC molecules expressed only on specialized antigen-presenting cells
4) Class II molecules also play a major role in allograft rejection
5) Class II MHC molecules present peptide antigens to CD4 T cells
6) Heterodimers of two chains, α and β - each chain is induced by a different gene
7) The β chain is the more polymorphic gene - only type β chains are tissue typed in class II

Question 15

For MHC molecules ___ helices form the groove and the __ sheets form the bed of the cleft

Answer 15

α;β

Question 16

Polymorphisms in MHC I and MHC II

Answer 16

• Occur in α helices and in β sheets of the heavy chain for class I MHC
• Occur in α helices and in β sheets on the β chain for MHC II

Question 17

Size limits for peptides in class I and II

Answer 17

Class I: 8-10 residues

Class II: 12-16 residues although they can be as long as 30+ residues

Question 18

Features shared by all class I peptides

Answer 18

N-term, C-term, peptide backbone

Question 19

Loose constraints for peptide

Answer 19

Certain amino acid residues are anchor residues, the rest can vary

Question 20

Estimated number of distinct peptides that can bind to each class I MHC molecule

Answer 20

> 1000

Question 21

Benefits of polymorphism

Answer 21

Although one virus can escape efficient presentation on antigen on a given individual’s 6 MHC molecules, it is hard to imagine a virus escaping presentation on all 1000 allelic variants within the population

Question 22

A high percentage of people who do not respond to Hepatitis B vaccine have HLA-DR7 and HLA-DR3 - why?

Answer 22

Homozygotes for these two haplotypes are found almost exclusively in the non-responder (NR) population
Antigen presenting cells (APC) of NR are defective in the uptake of HBsAg and they are unable to present this AG adequately (T-cells are defective in recognizing this antigen)

Question 23

Ankylosing Spondylitis

Answer 23

An inflammatory, possible autoimmune disease of vertebral joints
The HLA-B27 tissue type, while not causing AS, does predispose individuals with the B27 tissue type to developing AS - increases the chances by 100 fold