Lecture 12 Flashcards
what is the MHC complex locus called in mice? what chromosome?
H2
chr 17
what is the MHC complex locus called in human? what chromosome?
HLA
chr 6
how big the MHC locus?
7 million bp
what are 2 genes involved in MHC that are not on the same chromosome as MHC?
B2m and Ii
how are the diff MHC classes organized in the locus?
in clusters
describe beta chain in HLA-DR
2 beta chains in HLA-DR
what is unique about HLA-DM and DO?
non-classical class II molecules
since many genes involved in antigen processing are found on the human MHC locus, what is the significance?
the genes were co-selected during evolution
what is an example of non-MHC genes that are found in the human MHC locus?
complement protein genes
what is encoded in Class I besides HLA-A/B/C?
non-classical classIb genes –> HLA-E/F/G
what is a common inducer of MHC locus genes?
IFN
example of a gene induced by IFN-gamma and its role?
ClassII transactivator (not in MHC locus) induced by IFN-gamma to drive class II transcription
2 ways that MHC genes increase diversity?
- polymorphism
- polygeny
what is polymorphism?
many variations of MHC genes (i.e. alleles) at the same locus
what gene in MHC II is most polymorphic?
beta chains
what MHC class is the most polymorphic?
MHC I
which 2 MHC genes are less polymorphic?
HLA-DRalpha and H-2Ealpha
what is a consequence of polymorphism introducing many alleles for MHC I and MHC II?
unlikely to be homozygous –> therefore can present many Ag
what is a haplotype?
given combo of MHC alleles on 1 chromosome
what is polygeny?
many copies of a gene is possible
describe the type of dominant expression of MHC alleles
codominant –> all expressed at same time
evolution of MHC
MHC co-evolves with pathogens
2 types of polymorphism
- polymorphism within a population
- polymorphism within an individual
what is the name for polymorphism within a population?
Negative Frequency Dependent Selection
what is negative frequency dependent selection?
puts pressure to maintain rare alleles
why do we want to keep rare alleles?
pathogen can mutate to evade allele that is common, but then rare allele gives resistance –> keeps us unpredictable
what is the name for polymorphism within an individual?
heterozygous advantage
allelic variations lead to different _______ of MHC
allelic variations lead to different isoforms of MHC
how many aa can be different btwn MHC isoforms?
up to 20 aa different
what is different btwn MHC isoforms?
structure is unaffected, just the peptide binding cleft is affected
what part of the peptide binding cleft is different btwn MHC isoforms?
anchor residues
is it possible for Ag processing not to generate peptides that bind our MHC?
yes if homozygous –> fewer peptides can be presented (common in inbred animals)
in which instance can it be useful to predict peptide anchor residues?
vaccine design –> peptide anchor residues that allow for improved presentation will increase immune response
what is the consequence of MHC isoforms having diff anchor residues?
can bind diff peptides
what is required for TCR to be stimulated?
- matching MHC
- matching antigen
what is alloreactivity?
primary T cell response against allelic variants of MHC in the species
what occurs in direct allorecognition?
non-matching MHC is presented to T cell –> no restriction so will mount T cell response
what occurs in indirect allorecognition?
matching MHC presents non-matching MHC as its peptide to T cell –> presented by correct MHC and will induce T cell response
what are MHC congenic mice?
genetically identical except at MHC locus
what do MHC congenic mice allow for? (2)
- to compare biological effect of diff alleles in the same genetic background
- compare effect of given allele in diff genetic backgrounds