L18 - Major Histocompatability Complex Flashcards
(17 cards)
what is the MHC locus
the major histocompatability complex locus codes for proteins that present peptides to T-cells for an immune response
= found on chromosome 6 in humans
what chromosome and arm is the HLA/MHC loicus found in humans
6p21
MHC class 1 molecule structure
2 polypeptide chains; alpha and B2-microglubulin
Alpha chain has 3 domains: a1,a2 and 13
a1 and a2 form the peptide-binding cleft
MHC class 2 structure
2 polypetide chains - alpha and beta
each have 2 domains (a1 +a2) and (b1 and b2)
a1 and b1 form petide binding cleft
which MHc is present on all nucleated cells
MHC 1
what is polymorphgism and how does it describe MHC molecukes peptide bidning cleft
differeneces in alleles between people affect which peptides can bind
differences in peptides bound by MHC molecules
MHC 1:
short peptides
bind at terminal ends of peptide
endogenous/intracellular peptides
MHC 2:
longer peptides
binds ALONG the peptide
exogenous - extracellular proteins
summarise peptide laoding onto MHC class 1
intracellular antigens/peptides
- ubiquitinated proteins are degraded by proteososmes in cytoplasm
- newly synthesised MHC class 1 molecules helf in the ER form the Peptide-Loading Complex (PLC)
- PLC binds to degraded peptide and migrates to surface for presentation
= slef and non-self antigens are presented by MHC-1
= self reactive T-cells are removed during T-cell development
what type of cells are MHC found on
professional antigen presenting cells
- dendritic cells
- macrophages
- B cells
summariser peptide loading onto MHC-2 - 5 steps
extracelluklar antigens
- antigen is engulfed and degraded inside acific endosome by proteases
- vesicles containing MHC-2 fise with vesicle with broken down peptides
- CLIP protein blcoks binding of MHC-2 to peptide
- binding of HLA-DM removes CLIP allowing peptide to bind
- MHC with peptide migrates to surface for presentation
why is there such a diverse set of HLA/MHC molecules expressed on each human cell - 3 points
genetic polymorphism
co-dominat expression
gene combinations and recombination
what type of T-cells do each MHC class present too
MHC-1:
CD8 –> cytotoxic lysis of infected or tumour cells
MHC-2:
CD4 –> herlper cell functions such as = cytokine production,macrophage activation, T cell or B cell activation
describe the polygenic/polymorphic feature of HLA/MHC
There are multiple different HLA genes and each encodes a different MHC molecule
→ MHC-1 (HLA-A,HLA-B,HLA-C) each molecule is made from one of thse alpha genes and a beta chain
→ MHC-2 each molcule is amde from one alpha chain but there is also different beta chains = even more MHC possibilities
= chains can mix and match by recombination events
polymorphism:
allelic differences in the HLA genes
–> For example, the HLA-B gene alone has thousands of variants.
define co-dominance and how does it affect HLA molecules
Alleles are expressed simultaneously
= You inherit one set of HLA genes from each parent
= doubles the number of different HLA molecules a person can present (can choose HLA-A maternal or paternal)
= increasing the range of peptides that can be displayed.
name 1 other gene that is found on chromsome 6 HLA locus
TAP1 and TAP2 - antigen proscessing pathway
= involved in forming heterodimer in ER membrane and pumping degraded peptides into cytosol to bind to PLC
what 2 properies are HLA genes
polygenic:
multiple class 1 and 2 genes that can combine to produce different molcules
polymorphic:
variants of each gene = the most polymorphic genes known
what is it nealy impossible to find when comparing 2 individuals when looking at HLA
2 individuals expressing the same HLA molecules
= population diversity = immune protection
