MHC Flashcards
Ž - Describe the structure of MHCI.
alpha 1 - 3 + beta2-microglobulin domain
peptide-bining groove between a1 and a2, closed on both ends
peptide 8-10aa, attached via anchor residues on both ends, middle part arches up and away from MHC surface
Ž - Describe the structure of MHCII.
alpha and beta chain
peptide binding groove between a1 and b1
13-18 aa, binding by conserved residues along the length of the peptide, which is held at constant elevation above the floor of the groove
Ž - Which peptides, besides self-proteins degraded in (immuno)proteasome are loaded onto MHCI?
DRiPs = defective ribosomal products
= incorrectly translated proteins
e.g. from introns, improperly spliced mRNAs, frameshifts, misfolded proteins
Ž - Which proteins are crucial for presenting peptides on MHCI?
TAP1 and 2
Ž - What is the function of ERAAP?
shortening the peptides produced in the cytosol (and trasported into RER lumen by TAP) so that they can be presented on the MHCI
Ž - What is a haplotype?
a set of genetic determinants located on a single chromosome
Ž - What creates the variability in MHC in the population? How many different MHC molecules does an individual express?
many different alleles known
+ great majority of people is heterozygous for MHCs
+ MHC molecules are expressed codominantly from both copies of the DNA (combinatorial diversity)
leads to 1 person having 6 MHCI and 6/8 MHCII
Ž - What can influence and change MHC expression? What can cause different intensity of immune response to the same Ag between individuals?
- genetic regulatory components (promotors upregulate expression during infection)
- viral interference (viruses can shut down MHCI expression)
- cytokine-mediated signaling (cytokines can up/downregulate expression)
different capability to present antigens on specific MHCs an individual posesses
Ž - What is MHC restriction?
ability of T cells to recognize peptides only in context of self-MHC alleles
Ž - Which pathway leads to presenting antigens on MHC I and II?
I = cytosolic/endogenous II = exogenous
Ž - Describe the endogenous antigen processing pathway.
self proteins are processed by (immuno)proteasomes
transported to ER via TAP
shortened by ERAAP if necessary
loaded onto MHCI, which has to be prepped too:
- expressed in RER lumen
- stabilized and properly folded by calnexin and ERp57
- calnexin exchanged for b2-microglobulin
- tapasin and calreticulin added
- all chaperons dissociate when peptide is bound to the groove
MHCI:p is transported from RER to GA to plasma membrane
Ž - Describe the exogenous antigen processing pathway.
MHCII expressed in ER, binding groove blocked by invariant chain
MHC:InvCh routed through GA to endocytic compartments
invariant chain is clipped, only CLIP left
when fusing of the vesicle with endocytic vesicle, HLA-DM mediates exchange of CLIP for Ag peptide
MHCII:p is transported to plasma membrane
Ž - Why is cross-presentation so important?
to generate CTL immunity: this way, DCs can present exogenous pathogens on MHCI to prime CD8+ responses which will kill infected cells
