23 - MHC Flashcards
what are MHC molecules?
cell surface glycoproteins
highly polymorphic
what does the MHC do?
enables T cells recognition of Ag on cell surfaces
MHC I - CD8+
MHC II - CD4+
encoded by HLA genes
what are HLA?
human leucocyte antigens
what are the 2 types of MHC?
class I class II
- on different cell types
- bind antigens from different sources
- inherit 1 set from each parent
what HLA are MHC I?
HLA-A
HLA-B
HLA-C
what HLA are MHC II?
HLA-DP
HLA-DQ
HLA-DR
where is the HLA locus found?
on chromosome 6
MHC I structure
- heterodimer
- 3 alpha domains: a1,2,3
- 1 beta domain: b2 microglobulin
- binds 8-10 AA
- alpha1&2 domains form peptide binding region
- alpha3 is transmembrane domain
- beta2 microglobulin is not with the HLA complex
- polygenic - can bind lots of different antigens
MHC II structure
- 2 transmembrane domains: alpha2 and beta2
- alpha1 and beta1 form peptide binding region
- binds 13-24 AA
- beta chains different to the beta microglobulin in MHC I
where are MHC I expressed?
by most nucleated cells
where are MHC II expressed?
only on specialised immune cells - APCs
what do MHC I bind to?
CD8+ cytotoxic cells
what do MHC II bind to?
CD4+ T helper cells
peptide binding grooves of MHC I and II
MHC I is much smaller and doesn’t open as wide so doesn’t allow large peptides to bind
APCs are the only cells that can express both classes
what are endogenous antigens?
proteins made in the cytoplasm
presented by MHC I
what are exogenous antigens?
proteins made outside cell or in vesicles
presented by MHC II
endogenous peptide presentation by MHC I
1) antigen synthesised in cytoplasm
2) protein cleaved to peptides by proteasome
3) peptides transported to ER by TAP
4) peptides bind to MHC I molecules
5) MHC-peptide complex transported to cell surface
exogenous peptide presentation by MHC II
1) MHC II molecules in ER have invariant chain
2) MHC II moves from ER to vesicles - invariant chain broken down
3) antigen engulfed by APC
4) protein cleaved to peptides by proteases
5) vesicles with peptides fuse with vesicles with MHC II in
6) MHC II binds peptide fragments
7) MHC-peptide complex transported to cell surface
how does the TCR signal?
activation of CD3 complex needed to activate signalling cascade
ITAMs are vital in sending signal cascade to nucleus to activate transcription of cytokines
residues phosphorylated when something binds which activates cascade
what are ITAMs?
immune receptor tyrosine-base activation motifs
how is MHC recognition by T cells stabilised?
by the co-receptors CD8+ and CD4+
how many peptides can each MHC bind?
a single one at a time
can potentially bind different peptides though
what is the sniff test?
if someone has a different MHC molecule to you, you are more likely to be attracted to them
it is also known to be heightened during ovulation
contraception can affect this
