MHCs

Question 1

basic definition of an MHC

Answer 1

Show protein antigens to T-cells & bind TCRs. Coded by HLA genes.

Question 2

MHC I: where? function? HLAs?

Answer 2

Where: all nucleated cells (no RBCs)
Function: present intracellular antigens to CD8+ (CTLs)
HLAs: A,B,C

Question 3

MHC II: where? function? HLAs?

Answer 3

Where: APCs & thymic epithelial cells
Function: present extracellular antigens to CD4+ (Th, Treg)
HLAs: -DP, -DQ, -DR

Question 4

Intracellular (MHC I) vs extracellular (MHC II) antigens- examples?

Answer 4

Intracellular = endogenous (viral, cytosolic proteins)
Extracellular = exogenous (bacterial proteins)

Question 5

Where are the HLA genes? Order?

Answer 5

Chromosome 6.
Class II (DP, DQ, DR), 
Class III (C4, factor B, C2, lymphotoxin, TNF-allpha),
Class I (B, C, A)

Question 6

Structure of MHC I

Answer 6

1 long chain (alpha chain with 3 domains; alpha_3 is non-polymorphic) & 1 short chain (beta-2-microglobulin; non-polymorphic)

Question 7

What anchors MHC I to the cell membrane?

Answer 7

alpha-3 domain of the alpha-chain

Question 8

Size/binding location of peptides presented by MHC I

Answer 8

Endogenous peptides, 8-9 AAs long (closed alpha-helices).

Groove is in the alpha_chain of the MHC.

Question 9

Size/binding location of peptides presented by MHC II

Answer 9

Exogenous peptides, 14-15 AAs long.

Binds between the alpha_1 and beta_1 subunits.

Question 10

Peptide binding groove protein structure shared by MHC I & MHC II

Answer 10

2 alpha helices (closed ends in MHC I, open in MHC II) and a beta-sheet floor. Anchor sites in these residues determine what binds.

Question 11

Endogenous (MHC I) antigen processing pathway

Answer 11

1) Ubiquitination of endogenous antigens
2) Fed to immunoproteasome
3) TAP1 & TAP2 bring peptides into the RER
4) MHC & peptide bind, bud off from RER, exported to cell membrane

Question 12

Exogenous (MHC II) antigen processing pathway

Answer 12

1) Endo/phagocytosis bring antigen into the APC, enzyme degredation
2) Antigen vesicle fuses with MHC II vesicle from the ER, where MHC II is blocked with Ii (invariant chain) to prevent endogenous antigens from binding
3) Enzymes remove most of Ii, leave behind “CLIP”
4) “Peptide exchange”: DM & DO remove CLIP, insert peptide to MHC II.
5) Vesicle goes to cell surface

Question 13

TAP1 & TAP2

Answer 13

Transporters Associated with Antigen-Processing.

Proteins that span the ER, bring in processed peptides from cytoplasm to bind with MHC Is.