MHC I Flashcards
Where is MHC-I expressed?
- all nucleated cells
- expressed at higher levels on immune cells and can be induced by IFNg
What kind of peptides does MHC-I present?
exogenous peptides - foreign or self
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?
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
How is the B2-microglobulin attached to the alpha chain in MHC-I, and what does it do?
non convalently bonded
stabilizes and helps get MHC-I onto the cell surface
Where is MHC-II expressed?
- primarily found on the surface of pAPCs (DC, B cells and macrophages)
- some other cells (e.g. thymic epithelial cells)
What kind of peptides does MHC-II present?
Exogenous peptides (self or foreign)
How are exogenous peptides brought into the cell (3 methods) and which process do B cells favour?
- RME (B cells favour)
- pinocytosis
- phagocytosis
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?
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
What are the two primary differences between MHC-I and MHC-II? What is a similarity?
Similarity: structurally similar
Differences:
1. cleft structure - open vs. closed
2. where the peptides come from
Where are the human classical MHC genes located?
chromosome 6
What is a haplotype?
Collection of MHC genes on one chromosome
What is a consequence of MHC gene region being densely packed with genes?
not a lot of recombination during meiosis
What are human MHC-I and MHC-ll genes referred to as?
HLA - human leukocyte Ag
What are the three classical human MHC-I genes (alpha chain), and where is B2M located?
HLA-A, B and C
B2M is on another chromosome
What is the non classical human MHC-I gene HLA-G important for?
protects the fetus from rejection by mom
What are the three classical human MHC-II genes (alpha and beta chain)?
HLA-DP, DQ, DR (note: can have multiple chains for some genes)
What is the non classical human MHC-II gene HLA-DM important for?
involved in peptide loading onto classical MHC-II molecules
What are some other genes in the human class II region, and what is there importance?
LMP2, TAP1, and TAP2 are important for Ag presentation
What are some human class III genes that are located in the MHC region of chromosome 6?
cytokine (TNFa) and complement (C2 and C4b)
Where is the mouse MHC region located?
chromosome 17
What are mouse MHC genes called?
histocompatibility-2 genes (H2)
What are the three classical mouse MHC-I genes?
H2K, H2D, H2L
What are the two classical mouse MHC-II genes?
H2A and H2E
What other genes are included in the mouse MHC region?
genes for: cytokines, complement and Ag processing proteins
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
- polygenic
- polymorphic
- co-dominant expression
multiple MHC proteins are simultaneously expressed on the surface of each cell
What does it mean to be polygenic? How are human MHC molecules polygenic?
polygenic = multiple genes for each molecule
humans have 3 classical MHC-I and 3 classical MHC-II genes + 2 alleles of each
How are human MHC molecules polymorphic? And what are some consequences of these polymorphisms? Are classical or non-classical MHC genes more polymorphic?
- 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
Where are the polymorphisms in MHC-I and why?
more varaiblity found in a1 and a2 than a3 -> a1 + a2 = peptide binding cleft -> allows more variability in the peptides presented
Why is there more diversity in MHC-II expression than MHC-I despite having a similar number of genes and polymorphisms?
an alpha chain from mom can pair with a beta chain from dad and vice versa
How can individual classical MHC alleles present multiple peptides?
peptides presented by individual MHC alleles have similar features
What are anchor residues and what kind of binding does this lead to?
- 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)
What are the anchor requirements for MHC-I?
- 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
Because the ends of a MHC-I binding groove are closed how does this affect the peptide postion?
larger peptides form a bulge because termini anchor residues at the closed ends of MHC-I
What are the anchor requirements for MHC-II?
- 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
Because the ends of a MHC-Il binding groove are open how does this affect the peptide position?
The peptide is at a constant elevation (lies flat)
