11. MHC Flashcards
what are MHCs?
processed microbial proteins
what does the display of MHC instigate?
cell-mediated response
which cells can only target and present Ag from phagocytosed microbes?
APCs
difference between Ag recognised between a) BCR and b)TCR
a) protein, lipid, NA - linear and conformational epitopes
b) MHC on APC - linear epitopes
what is the Ag attached to in a)BCR b)TCR
a) variable H+L chains
b) Variable regions of alpha and beta chains
what causes signalling in
a) BCR
b) TCR
a) Ig-alpha and Ig-beta
b) CD3 protein
structure of binding site in
a) BCR
b) TCR
a) 3 of each CDR’s in Variable heavy and light chains
b) 3 of each CDR’s in variable alpha and variable beta chains
describe affinity of binding in
a) BCR
b) TCR
a) increases after Ag binding
b) very high- due to specificity
on rate of
a) BCR
b) TCR
a) fast
b) slow
off rate of
a) BCR
b) TCR
a) variable
b) slow
7 similarities between BCR and TCR
- part of Ig superfamily structure
- Have N terminals where Ag bind at V regions
- Located on cell surface
- Work by signalling other molecules in receptor complex
- 3 CDR’s
- similar receptor diversity
- VDJ gene segment structure
After an Ag has attached to a TCR - how is the signal transduced?
via ITAM tails - immuno-receptor tyrosine-based activation motifs.
3 ways TCR diversity is achieved?
- somatic recombination in germline gene pools
- Junctional diversity
- Transcription and RNA processing
what 2 processes are there in Abs which dont occur in TCR - in terms of diversity?
- class switching
2. Ag driven hypermutation
which cells express MHC I?
nucleated cells and DC in secondary LT
which cells express MHC II?
APC - dendritic, B cell, Macrophage
what type of peptides do MHC I represent?
endogenous
what type of peptides to MHC II represent?
exogenous- have been phagocytosed
describe MHC I structure
- 3 alpha domains - 1,2,3,
- B2 domain - not covalently associated to alpha chain
- a1 and a2 - polymorphic - between is peptide binding cleft
- b2 and a3 = Ig like
- a3 - binds to CD8
describe MHC II structure
- 2 chains - 1 alpha, 1 beta, a1 a2 b1 b2
- a1 and b1 - polymorphic - between is peptide binding cleft
- a2 and b2 = Ig like
- b2 = binds CD4
difference in peptide binding groove between MHC classes
I - polypeptide chain only bound at edges
II - polypeptide chain bound along the whole length of MHC
8 steps in processing of intracellular cytoplasmic pathogens
- Viral pathogen enters cytoplasm
- viral proteins are unfolded, ubiquitanised and broken down by proteases
- viral fragments sent to ER by TAP I and TAP II - transporting associating proteins - further trimming
- newly sythesised MHC - stabilised by chaperone and attached to linker protein (tapasin) - allows them to be located by peptide
- MHC forms complex with viral fragments
- complex transported by secretory network - via vesicles
- complex presented on cell surface
- MHC I detected by CD8 +T cells
8 steps in processing of intracellular vesicular pathogens
- APC engulfs Ag
- phagosome fuses with lysosome = phagolysosome
- lytic enzymes break down ag into fragments
- phagolysosome fuses with vesicle containing MHC II
- Class II invariant chain peptide (CLIP) is removed from the MHC II region via HLA-DM. this molecule replaces it with the Ag fragment.
- transported to cell membrane via secretory network
- recognised by CD4+ T cells
describe the specificity of MHC molecules
broad
5 features of MHC complex
- broad specificity
- very slow off rate - enough time for T cells to recognise
- can only bind/display 1 Ag at a time
- only presented on cell surface when bound to a fragment - stable
- only present protein/peptide Ag
on which chromosome are the MHC genes?
6
MHC I genes code for which 3 proteins?
HLA-A
HLA-B
HLA-C
MHC II genes code for which 3 proteins?
HLA-DP
HLA-DQ
HLA-DR
what type of protein does MHC III code for?
complement
what are the main antigens recognised in transplants?
MHC
describe structure of Ig domain
2 x anti-parallel beta pleated sheets
joined by disuphide bond
