Lecture 9 - MHC Flashcards
What does the TCR recognise?
The combined shape of the MHC and antigen
Number of extracellular domains possessed by MHC
Four
Is the b2-microglobulin gene in the HLA locus?
No
On a different chromosome
Is the b2-globulin chain covalently linked to MHCI?
No
Length of peptides recognised by TCR
8-12aa
Regions making up MHCI peptide-binding region
Alpha1, alpha2
Regions making up MHCI Ig-like domain
Alpha3, B2-mocroglobulin
Size of alpha1, alpha2 and alpha3 domains
Each is 90aa
Regions of an MHC molecule 1) 2) 3) 4)
1) Antigen-binding region
2) Ig-like region
3) Transmembrane region
4) Cytoplasmic region
Shape of peptide-binding cleft
Base of beta sheets
Surrounded by two alpha helices
Chains of MHCI
Heavy chain - alpha1, alpha2, alpha3
Light chain - b2-microglobulin
MHCII structure
No heavy or light chains
Two equal chains, one made of alpha1, alpha2, the other made from beta1, beta2
Antigen-binding site of MHCII
Alpha1, beta1
Are the alpha1 and beta1 regions of the MHCII antigen-binding cleft covalently linked?
No
Differences between MHCI and MHCII 1) 2) 3) 4)
1) MHCI has b2-microglobulin
2) MHCI has a heavy and light chain. MHCII has two equal-length transmembrane proteins.
3) MHCI interacts with CD8. MHCII interacts with CD4
4) MHCII can bind slightly larger proteins than MHCI
At what orientation does TCR bind to MHC?
At a diagonal angle
Ensures maximum contact
Does TCR contact mostly MHC or antigen?
TCR makes most contact with MHC surface
TCR specificity
Specific to both antigen and MHC
Does MHC expression change in cells?
Yes.
Upregulation during immune response
MHC human locus
Human Leukocyte Antigens (HLA) locus
Mouse MHC locus
H-2 locus
Structure of human HLA locus
2 regions, each with 3 genes
1 region is MHCII, 1 region is MHCI
HLA MHCII genes
DP
DQ
DR
HLA MHCI genes
B
C
A
H-2 locus structure
2 class II genes flanked by 2 class I genes (1 on each side)
H-2 locus class I genes
K
D
H-2 locus class II genes
I-A
I-E
Genes in I-A and I-E regions
I-A and I-E each have an alpha chain and a beta chain gene
Genes in K and D regions of H-2
K has one alpha gene
D has two alpha genes
Why does the D region of H-2 have two alpha chain genes?
Gene duplication and divergence
How are MHC alleles expressed?
Codominantly Both alleles (one from each parent) are expressed
Location of HLA locus
Chromosome 6
Location of b2-microglobulin gene
Chromosome 15
Maximum number of MHCI types expressible on a cell surface
6 (3x different types on each chromosome)
Minimum number of MHCI types expressible on a cell curface
3
If B, C and A are homozygous
Which MHC has more variety?
MHCII
Alpha and beta chains can be promiscuous
Stability of hybrids isn’t favourable, so most MHC on cell surface are unhybridised
Outcome of MHC polymorphism
Allows or prevents binding by certain TCRs