Antigen Processing and Presentation Flashcards
what is the most potent APC?
dendritic cells
function of dendritic cells?
- capture Ag and process into small peptides to bind to MHC
- present Ag to activate T cells
- support the functions of other cell s
which cells are professional APC?
- macrophages
- dendritic cells
- B cells
how do B cells act as APC?
ingest antigens and display them on MHC II to the CD4 helper cells in lymphoid tissue to generate humoral immune response
how do DC capture proteins/Ag?
endocytosis! which then binds to phagosome
which MHC binds to CD4
MHC II
which MHC binds CD8?
MHC I
which cells contain MHC I?
all nucleated cells
structure of MHC I?
3 segmented alpha chain, 1 segmented beta globulin
what cells contain MHC II?
only DC, macrophages, B cells
structure of MHC II
2 alpha chains and 2 beta chains
what antigens do MHC I display?
endogenous Ag
what antigens do MHC II display?
exogenous Ag
1st step of endogenous Ag processing
proteasome and immunoproteosome take up ubiquinated proteins to make peptides
when is proteasome active?
active in the absence of infection
what does proteasome do?
degrades cytosolic proteins that are damaged, poorly folded or no longer needed
what induces immunoproteosome?
IFN gamma that was produced by NK cells or T cells (Th1)
how are peptides produced by proteasome and immunoproteosome transported out of the ER?
TAP transports peptides across ER membrane into ER lumen via ATP
what occurs if there is a TAP deficiency in a patient?
- chronic respiratory infections from birth
- minimal CD8 response
- little MHC I on cell surfaces
what does calnexin do?
stabilizes construction of MHC I ALPHA chain
where are the alpha chain and beta 2 microglobulin chains of MHC I produced?
ER
what occurs once the B2micro chain and alpha chain come together?
ERp57 tapasin-Calreticulin helps it associate with TAP (so peptides can come through TAP)
what is the last thing that stabilizes MHC I?
peptide binding!
what occurs once MHC I binds peptide?
tapasin is released, and signal peptide is added to the loaded MHC I to drive it to cell surface
what does ERAP do?
trims oversized peptides into manageable lengths for MHC I
what must occur first before MHC II molecules are begun to be made?
endosome with Ag fuses with phagosome and undergo acidification to activate acid hydrolase where peptide can be unfolded and degraded
what function does the invariant chain do when the MHC II alpha and beta chains are generated?
- blocks MHC II peptide binding site so it doesn’t bind ER peptides
- stabilizes MHC II
- directs vesicle transport
how is invariant chain released from MHC II?
cathepsin S and proteases cleave it, but leave CLIP
what component remains bound to MHC II after invariant chain is released from MHC II?
CLIP (class II associated invariant chain peptide)
what occurs once invariant chain is clipped?
the MHC II compartment vesicle fuses with endosome/phagolysosome with the peptides in them
what finally removes CLIP from MHCII binding site?
HLA-DM removes CLIP so that peptides can bind
what triggers HLA-DM release from MHCII?
right peptide binding to MHC II
what occurs once HLA-DM is released?
HLA-DO binds to it so it doesn’t try and bind to MHC II again
what effect does IFN gamma have on this process?
increased HLA-DM expression and increased Ag presentation which directly increases the number of MHC II molecules
what cells can undergo cross presentation of Ag?
dendritic cells
steps of cross presentation
- Ag export from phagosome to cytosol
- Ag transport into phagosome
- phagosome degradation of Ag
why is cross presentation a thing?
if an antigen is presented exogenously, you want them to be killed by CD8, so you would need MHC I presentation, which is done endogenously. therefore, must uptake and degrade them so they can be shown to MHC I – for memory generation
where do the DC live that do cross presentation
lymph node
what does cross dressing actually do
transfer of preformed MHC peptide from the migrating DC to the Lymph node DC to present
describe direct presentation
endogenous Ag binds to endogenous MHC I
describe cross presentation
exogenous Ag binds to endogenous MHC I
describe cross dressing
exogenous Ag binds to exogenous MHC I
what increases alpha and beta2microglobulin and TAP expression for MHC I?
IFN alpha, IFN beta, IFN gamma
what increases HLA-DM, HLA-DP, HLA-DQ, HLA-R and invariant chain?
IFN gamma
how are HLA genes inherited?
both sets of genes are expressed, meaning that maternal and paternal genes are inherited
benefit of HLA inheritance?
ensures that a greater number of pathogen derived peptides will be presented during any infection (any infection your parent has had, you have the HLA for that)
what is linkage disequilibrium?
when haplotypes of HLA exist that are due to meiotic recombination events (random resistance to disease_
how are new MHC alleles derived?
mutations from infections/pathogens resulting in natural selection (for survival advantage)
what does HLA-E do?
is a MHC class Ib molecule that engages NK cells
what occurs if HLA-E interacts with NKG2A or NKG2B?
inhibition of NK
what occurs if HLA-E interacts with NKG2C?
activation of NK
what occurs if there is a MHC class I loss on cells?
upregulate HLA-E and express NKG2A and NKG2B to inhibit NK so they don’t kill you
how are fetal cells not destroyed by mother’s NK cells?
placental and fetal cells express HLA-G, which binds to KIR2DL4, inhibiting NK cell destruction
what does MICa and MICb do?
binds NKG2D on NK cells, NKT cells, and cytotoxic lymphocytes and overrides the inhibitory signal from MHC I on NK = NK cell activation, aka activated and killing things
what is MHC restriction?
where TCR recognizes Ag on self MHC’s but not on new or non-self MHC - occurs during organ transplant rejection
what helps increase diversity of peptide binding in MHC?
number of AA residues in binding pocket of MHC bind, leaving other peptides to contact TCR bulge
