Mhc Genetics/variation And Disease Flashcards
What do MHC bind
Ag epitopes
Who do they present to
T cells either cd8 or cd4
How is central self/immune tolerance achieved
Negative and positive selection in thymus for T cells
Negative In bm for b cells
Which gene allows ag like insulin to be expressed in thymus to stop autoimmunity
Aire
How is peripheral immune tolerance different
That is tolerance in lymph nodes not primary lymphoid organs
What types of cells made in thymus damp down T cells escaping selection
Fox p3 tregs
What type of ag do mhc 1 present to cd8
Self ag if healthy, neo ag if cancer cells, foreign material in transplantation, viral if infected
How is peptides loaded on MHC 1 after proteasomes deg
Via tap enter rer and tapasin helps loading
How are MHC 2 different
Only on b cells, mac and dcs
Present to CD4
Only exogenous ag
Explain trafficking of MHC 2
Mhc2 with invariant chain meet ag fragments in a vesicular compartment MIIC (late endosomal) where proteases which cleaved ag cleave the invariant chain. Clip is then remaining and hla-dm exchanged this with the peptide
Move to surface via vesicles
How are the 2 sets of hla genes inherited
As a haplotype
Which chain of MHC 1 is acctually encoded by hla abc
A chain (b2 micro globulin is on chr 15)
Which MHC holds smaller peptides
MHC 1 because closed ended (see more info on fr)
8-10 aa
What needs to form for MHC to be in reactive and stable
Pmhc complex is needed. Ie usually always presenting self ag but tolerant
What is the pMHC dependant on
The alleles a person inherits which is v diverse so more peptides presented
What confounding factors affect if peptides would bind
Tapasin, hla-dm available and ag availability
MHC are targets of immune evasion by pathogens. What is this
Where they mutate the peptides previously recognised and presented by the MHC alleles. If they mutate can’t recognise and present
Which hla class 2 gene can actually have more than 1 copy of b chain so increasing diversity of variations
Hla dr
Give 3 ways MHC genetics allows diversity
Polygenic (3 pairs of genes each)
Codominance of maternal and paternal alleles
Polymorphisms mainly in the binding groove
What does codominance mean
Both maternal and paternal alleles are expressed Same time same cell
Ie 2 forms of hla dp alpha chain etc
Which genotype will recognise and present more ag
Heterozygous
Why are mutations in MHC likely due to selection pressures rather than random
Because they always cause a significant change eg in AA sequence
Give an example of polymorphisms effects
Can affect peptide groove opening, tcr binding affinity , better stimulation of T cells (see fr)
How many MHC 1 and 2 molecules expressed on cells
If heterozygous 6 for MHC 1 and 8 for MHC 2 given dr can have 2 copies
