Linking Innate and Adaptive Immunity 4 Flashcards
do MHC always have an antigen when on the membrane?
yes
what are 2 examples of molecules that MHC Class I present?
- self proteins
- intracellular pathogens
how do endogenous pathogens enter the cell?
mediates its own entry –> uses receptors on the host
describe how peptides are produced in the endogenous pathway (3 steps)
- ubiquitin tags the protein
- protein fed to proteasomes
- peptide fragments produced
what is step 1 of the endogenous pathway?
MHC Class I folding in ER
- partly folded MHC I alpha chains x3 held in place by CALNEXIN
what is step 2 of the endogenous pathway? (3)
- MHC Class I released from calnexin
- CALRETICULIN and ERp57 push alpha and beta2 microglobulin together
- partly folded MHC I binds TAPASIN to link it to TAP
what occurs while MHC Class I is being produced in step 2 of the endogenous pathway?
endogenous proteins are being translated in cytosol
what is step 3 of the endogenous pathway? (3)
- polyubiquitinated proteins degraded by proteasome in cytosol
- peptide fragments are brought into ER by TAP
- ERAAP trims peptides that are too long to bind MHC
what is step 4 of the endogenous pathway? (5)
- peptide binds to peptide binding groove of MHC I
- MHC I folding is complete
- p:MHC I released from TAP
- p:MHC I passes thru golgi
- p:MHC I targeted for cell membrane
how are peptides generated in the exogenous pathway (MHC II)? 4 steps
- antigen taken up into endosomes
- endosome fuses with lysosome to make phagolysosome
- phagolysosome acidifies
- contents get degraded into peptides
what occurs at the same time as peptides are being generated in the exogenous pathway?
MHC II molecules are being produced and exported from ER in vesicles
where are MHC II molecules formed?
in ER
what is the invariant chain?
binds to the peptide binding groove/cleft of MHC
what is the role of invariant chain? (2)
A. guides the transport of MHC II to endosome
B. prevents peptides from binding to the groove too early
how does the invariant chain guide MHC II to endosome?
it has a tail in the cytoplasm with sorting signals to direct vesicles with MHC II to endocytic vesicles with peptides
describe the cleavage of the invariant chain. what does it eventually become?
cleaved in an acidified endosome to become CLIP
what is step 1 of the exogenous pathway? (2)
- invariant chain is in complex with MHC II in ER
- put into an endocytic vesicle
what is step 2 of the exogenous pathway? (2)
- endocytic vesicle acidifies
- invariant chain is cleaved, leaving CLIP bound to MHC II
what is step 3 of the exogenous pathway? (2)
- MHC II vesicle fuses with peptide vesicle
- CLIP blocks peptides from binding MHC II
what is step 4 of the exogenous pathway (4)
- HLA-DM binds MHC II
- CLIP releases from MHC II
- peptide binds MHC II
- p:MHC II targeted to cell surface
what does HLA-DM stand for?
Human Leukocyte antigen-DM
STEPS OF MHC I PATHWAY
- pathogen enters cell with host receptors
- ubiquitin tags protein for degradation
- In ER, CALNEXIN holds partly folded alpha chains in place
- Calnexin leaves
- alpha and beta interact due to ERp57 and CALRETICULIN
- MHC I binds TAPASIN to link it to TAP
- TAP brings peptide into ER
- ERAAP trims peptide
- peptide binds MHC I –> folding complete
- MHC I targeted to cell membrane
STEPS OF MHC II PATHWAY
- pathogen enters by phagocytosis into an endosome
- endosome fuses with lysosome
- vesicle acidifies to degrade antigen
- in ER, invariant chain binds MHC II at peptide-binding cleft to guide it to peptide vesicle and block unwanted peptides
- endosome acidifies to cleave li, leaving CLIP behind
- peptide and MHC II vesicles fuse
- HLA-DM binds MHC II and CLIP releases
- peptide binds MHC II
- MHC II targeted to cell membrane
