MHC I

Question 1

Where is MHC-I expressed?

Answer 1

• all nucleated cells
• expressed at higher levels on immune cells and can be induced by IFNg

Question 2

What kind of peptides does MHC-I present?

Answer 2

exogenous peptides - foreign or self

Question 3

What are the two chain that make up MHC-1, what domains interact with CD8, what domains make up the peptide binding groove, what is the size limit of the peptides (and what causes this) and where are Ig domains found?

Answer 3

MHC-1 = alpha chain + B2-microglobulin (B2m)

CD8 interacts with the alpha 3 domain

peptide binding groove = alpha 1 + alpha 2 + beta sheet

size limit of peptides = 8-10 a.a, this is due to the ends of the peptide binding groove being closed

Ig domains in a3 and B2m

Question 4

How is the B2-microglobulin attached to the alpha chain in MHC-I, and what does it do?

Answer 4

non convalently bonded
stabilizes and helps get MHC-I onto the cell surface

Question 5

Where is MHC-II expressed?

Answer 5

• primarily found on the surface of pAPCs (DC, B cells and macrophages)
• some other cells (e.g. thymic epithelial cells)

Question 6

What kind of peptides does MHC-II present?

Answer 6

Exogenous peptides (self or foreign)

Question 7

How are exogenous peptides brought into the cell (3 methods) and which process do B cells favour?

Answer 7

1. RME (B cells favour)
2. pinocytosis
3. phagocytosis

Question 8

What are the two chain that make up MHC-II, what domains interact with CD4, what domains make up the peptide binding groove, what is the size limit of the peptides (and what causes this) and where are Ig domains found?

Answer 8

MHC-II = alpha + beta chain

CD4 interacts with B2 and a2

peptide binding groove = both chains (2 alpha helices + 1 beta sheet)

size limit of peptides = 13-18 a.a, ends of peptide binding groove are open which allows larger peptides to extend out of the cleft

Ig domains found on a2 and B2

Question 9

What are the two primary differences between MHC-I and MHC-II? What is a similarity?

Answer 9

Similarity: structurally similar

Differences:
1. cleft structure - open vs. closed
2. where the peptides come from

Question 10

Where are the human classical MHC genes located?

Answer 10

chromosome 6

Question 11

What is a haplotype?

Answer 11

Collection of MHC genes on one chromosome

Question 12

What is a consequence of MHC gene region being densely packed with genes?

Answer 12

not a lot of recombination during meiosis

Question 13

What are human MHC-I and MHC-ll genes referred to as?

Answer 13

HLA - human leukocyte Ag

Question 14

What are the three classical human MHC-I genes (alpha chain), and where is B2M located?

Answer 14

HLA-A, B and C
B2M is on another chromosome

Question 15

What is the non classical human MHC-I gene HLA-G important for?

Answer 15

protects the fetus from rejection by mom

Question 16

What are the three classical human MHC-II genes (alpha and beta chain)?

Answer 16

HLA-DP, DQ, DR (note: can have multiple chains for some genes)

Question 17

What is the non classical human MHC-II gene HLA-DM important for?

Answer 17

involved in peptide loading onto classical MHC-II molecules

Question 18

What are some other genes in the human class II region, and what is there importance?

Answer 18

LMP2, TAP1, and TAP2 are important for Ag presentation

Question 19

What are some human class III genes that are located in the MHC region of chromosome 6?

Answer 19

cytokine (TNFa) and complement (C2 and C4b)

Question 20

Where is the mouse MHC region located?

Answer 20

chromosome 17

Question 21

What are mouse MHC genes called?

Answer 21

histocompatibility-2 genes (H2)

Question 22

What are the three classical mouse MHC-I genes?

Answer 22

H2K, H2D, H2L

Question 23

What are the two classical mouse MHC-II genes?

Answer 23

H2A and H2E

Question 24

What other genes are included in the mouse MHC region?

Answer 24

genes for: cytokines, complement and Ag processing proteins

Question 25

What are the three big properties of MHC molecules that makes their expression highly variable? What does this mean for the expression of MHC molecules on the cell surface

Answer 25

1. polygenic
2. polymorphic
3. co-dominant expression

multiple MHC proteins are simultaneously expressed on the surface of each cell

Question 26

What does it mean to be polygenic? How are human MHC molecules polygenic?

Answer 26

polygenic = multiple genes for each molecule

humans have 3 classical MHC-I and 3 classical MHC-II genes + 2 alleles of each

Question 27

How are human MHC molecules polymorphic? And what are some consequences of these polymorphisms? Are classical or non-classical MHC genes more polymorphic?

Answer 27

• multiple alleles exist for each classical MHC gene
• most polymorphic genes in humans
• often heterozygous of each gene (lots of diversity in the human population)
• classical MHC genes have greater diversity than non-classical

Question 28

Where are the polymorphisms in MHC-I and why?

Answer 28

more varaiblity found in a1 and a2 than a3 -> a1 + a2 = peptide binding cleft -> allows more variability in the peptides presented

Question 29

Why is there more diversity in MHC-II expression than MHC-I despite having a similar number of genes and polymorphisms?

Answer 29

an alpha chain from mom can pair with a beta chain from dad and vice versa

Question 30

How can individual classical MHC alleles present multiple peptides?

Answer 30

peptides presented by individual MHC alleles have similar features

Question 31

What are anchor residues and what kind of binding does this lead to?

Answer 31

• peptides bound have similar types of a.a.s at specific positions
• semi-promiscuous binding (although the anchor residues are fixed the other a.as can vary)

Question 32

What are the anchor requirements for MHC-I?

Answer 32

• usually hydrophobic a.a.s
• usually at the ends of peptides
• C-term residue is almost always an anchor residue
• NH3 and COO- termini of peptide also make important contacts with MHC-I

Question 33

Because the ends of a MHC-I binding groove are closed how does this affect the peptide postion?

Answer 33

larger peptides form a bulge because termini anchor residues at the closed ends of MHC-I

Question 34

What are the anchor requirements for MHC-II?

Answer 34

• anchor residues are more variable than class I peptides
• because peptide often extends out of MHC-II, the N and C terminal residues are not commonly anchor residues
• anchor residues more often found in the amino acids in the middle of the peptide

Question 35

Because the ends of a MHC-Il binding groove are open how does this affect the peptide position?

Answer 35

The peptide is at a constant elevation (lies flat)