MHC Flashcards
the only cells that can initiate a T cell response are ____
dendritic cells (DC)!!
T cells + antigen = no response until you add DC + loaded MHC
**DC are ONLY APC that can activate a naive T cell
T cells are activated by interaction of _____ on ______ and _____ on T cells
T cell activation:
MHC on APC (DC only!) + TCR on T cell
fill in the blank:
- CD8 T cells bind APC (DC cells) loaded with class ___ MHC
-CD4 T cells bind APC (DC cells) loaded with class ____ MHC
CD8 binds MHC I —> cytotoxic granule release [remember MHC I = endogenous/virus]
CD4 binds MHC II —> lymphokine release [remember MHC II = exogenous/bacteria]
why does it make sense that virtually all cells express MHC I?
MHC I is for endogenous antigens, very specialized for viruses
the immune system can’t keep surveillance of what’s INSIDE cells, so all cells need an “alarm” system to alert the immune system
basic structure of MHC I and II
MHC I: heterodimer of alpha heavy chain + beta2 microglobulin (helps alpha chain fold) …. bind shorter peptides
MHC II: heterodimer of alpha and beta chain …. bind longer peptides
what are the steps of the MHC II pathway (name the important players)? 6 steps
- endocytosis of antigen, cleave protein into peptides in endosome/lysosome
- Invariant chain (Ii): chaperone, helps MHC II fold, targets MHC II to endosome/lysosome, donates CLIP
- CLIP blocks peptide binding groove in ER (preserves binding groove, prevents peptides destined for MHC I from binding)
- endosomal/lysosomal proteases cleave invariant chain so only CLIP is left in MHC II groove
- HLA-DM (MHCII-like molecule) removes CLIP, loads peptide, makes sure it is high affinity
- exocytosis of MHC complex to surface
fill in the blanks of the MHC II pathway:
- endocytosis of antigen, cleave protein into peptides in endosome/lysosome
- ______: chaperone, helps MHC II fold, targets MHC II to endosome/lysosome, donates ____
- ____ blocks peptide binding groove in ER
- endosomal/lysosomal proteases cleave _______ so only ___ is left in MHC II groove
- _____ (MHCII-like molecule) removes ____, loads peptide, makes sure it is high affinity
- exocytosis of MHC complex to surface
- endocytosis of antigen, cleave protein into peptides in endosome/lysosome
- Invariant chain (Ii): chaperone, helps MHC II fold, targets MHC II to endosome/lysosome, donates CLIP
- CLIP blocks peptide binding groove in ER
- endosomal/lysosomal proteases cleave invariant chain so only CLIP is left in MHC II groove
- HLA-DM (MHCII-like molecule) removes CLIP, loads peptide, makes sure it is high affinity
- exocytosis of MHC complex to surface
before loading, where are MHC molecules found in the cell?
ER
exocytosed to surface after loading
*note that MHC I hang out in ER waiting to be loaded, but after MHC II formation, they go to the endosome/lysosome waiting to be loaded
how does a proteasome become an immunoproteosome? what do they do?
add IFNy (gamma)
immunoproteosomes create MHC I - friendly peptides (for binding/loading onto MHC I)
degrades ubiquitin-labeled proteins found in the cytoplasm
what is needed to transport endogenous antigens to the ER for MHC I loading? (3 things)
- TAP (Transporter associated with Antigen Processing): shuttle peptides from cytosol to ER (they cannot diffuse across ER membrane themselves)
- chaperone protein helps MHC I fold - brings beta2m (subunit of MHC I) to stabilize MHC I binding groove
- TAPASIN: bridge between TAP and MHC I, ensures high affinity peptides are loaded
self vs non-self is distinguished at the level of ____
T cells
basically, MHC I can load self peptides too, but T cells will make the decision
explain cross presentation in MHC I pathway
DC cells needed to activate T cells, but what if virus cannot directly infect DCs?
basically other cells (not DC cells) are infected with viruses and either antigens are presented via their MHC I or they die and release the antigens. DC cells detect this and then can present these same antigens by taking them up. THEN DC cells can activate T cells via MHC I
HLA genetic region - what are these genes and how is diversity generated
Human Leukocyte Antigen genetic region (aka human MHC): contains genes that encode proteins involved in antigen processing/presentation
each allele generates a different protein with unique peptide binding groove (via polymorphisms) - allows immune system to see broad set of peptides (with different peptide binding motifs)
**MHC I and II genes are polygenic (large variation between individuals)
what are the HLA genes for MHC I and MHC II
MHC I: HLA-A, HLA-B, HLA-C
MHC II: HLA-DR, HLA-DP, HLA-DQ (and sometimes HLA-DRB2)
how are HLA inherited?
haplotypes (blocks of HLA alleles) are inherited together
tons of alleles for each HLA
inherit a haplotype from each parent, so you get 6 alleles (3 genes, 2 different alleles of each)
*haplotype; physical grouping of genomic variants (or polymorphisms) that tend to be inherited together (in other words: haplotype is a combination of alleles from multiple loci on a single chromosome)
