MHC

Question 1

What do T-cell receptors bind?

Answer 1

They do NOT bind antigens directly
They bind processed peptides on the major histocompatibility complex (MHC)

The final ligand is a peptide-MHC ligand

Question 2

What are the two types of peptide-MHC ligands?

Answer 2

1. Peptide-MHC 1 - interacts with Cytotoxic T cells (CD8+)

2. Peptide-MHC 2 - interacts with helper T cells (CD4+)

Question 3

What are the functions of four general type of T-helper cells?

Answer 3

Th1 - inflammatory cytokine production - IFN-y, TNFa
Th2 - signal B cells for class switching
Th17- inflammatory cytokine production - IL-17
ThF - signal for B cells to expand in lymphoid follicles

Question 4

How are T cells and MHC involved in transplant rejection?

Answer 4

T cells will interact with foreign MHC molecules present on transplanted tissue

Question 5

Why is MHC polymorphism good and bad?

Answer 5

Bad because it makes tissue transplant difficult

Good because there is more ‘self-ness’ to each person which helps the population be resistant to many infectious agents

Question 6

What genes control MHC class 1 production? What part of the receptor is polymorphic vs not?

Answer 6

HLA-A, HLA-B, and HLA-C which are all highly polymorphic. These code the alpha chain which has three domains.

The beta2 microglobulin is coded by non-MHC loci, and is not polymorphic. It serves to stabilize the MHC Class 1 receptor so it can present peptide effectively.

Question 7

What genes control MHC class 2 production? What part of the receptor is polymorphic vs not?

Answer 7

HLA-DP, HLA-DQ, HLA-DR which are polymorphic. Each locus has A and B which code for alpha and beta chains which contribute equally to the MHC Class 2 receptor. Thus, there are 6 class 2 genes on each chromosome.

Question 8

How many HLA genes does each person have? What is their expression?

Answer 8

12, 6 from one parent and 6 from the other, which can all be different.

These are all co-dominantly expressed

Question 9

What does HLA-B*17 mean?

Answer 9

HLA-B gene for that person is allele group 17. Other numbers indicate specific protein substitutions / changes.

Question 10

How large is the peptide-binding groove of MHC Class I? Which alpha domain interacts with B2 microglobulin, and what else does it touch?

Answer 10

8-11 amino acids

Alpha3 interacts with the B2 protein, and also the CD8 molecule on T cells.

Question 11

What are anchor residues? How many on MHC Class 1?

Answer 11

2-3 positions of the processed peptide on MHC are critical in that they must have amino acids of a particular class in order to fit (i.e. positive charge, negative charge, hydrophobic, aromatic).

Question 12

What is the CD4 binding site on MHC Class 2?

Answer 12

Beta-2 domain

Question 13

How large is the peptide-binding groove of MHC Class 2? How many anchor residues?

Answer 13

13-30 amino acids, with 2-4 anchor residues

Question 14

What cells is MHC class 1 expressed on?

Answer 14

All nucleated cells

Question 15

What cells is MHC class 2 expressed on?

Answer 15

APCs, DCs, B cells, and thymic epithelial cells

Question 16

What cytokine increases antigen expression activities to induce MHC Class 2 expression?

Answer 16

Interferon gamma

Question 17

What is the pathway for antigen presentation on MHC Class 1? What proteins are involved in translocation to the ER?

Answer 17

Proteins are degraded by the proteasome (can be self or non-self). TAP-1 and TAP-2 transport proteins to the ER, where fragments become associated with the newly formed MHC Class 1. These peptides will be presented on the surface of the cell.

Question 18

What types of cells are targeted by MHC Class 1?

Answer 18

Those with peptides from intracellular pathogens / parasites whose proteins would’ve been broken down by the proteasome

Question 19

What types of antigens are targeted by MHC Class 2?

Answer 19

Foreign peptides which have been phagocytosed by an APC, serves to generate T helper cells.

Question 20

What is the mechanism of MHC Class 2 presentation?

Answer 20

MHC Class 2 is assembled in ER and stabilized by CD74.

CD74 degrades to CLIP after vesicle ships from Golgi.

Phagocytosed and acid-digested vesicle fuses with MHC vesicle, and HLA-DM mediates CLIP removal.

The immunodominant protein fragment will bind

Question 21

Can antigens bind to MHC at cell surface? Why might this not happen?

Answer 21

Yes they can, but it is rare since naked MHC molecules are unstable and cannot be transported to the cell surface

Question 22

What is cross-processing?

Answer 22

Pathways can overlap, and APCs can also express exogenous proteins on MHC Class 1