Nature of alloresponse and major histocompatibility antigens Flashcards
(47 cards)
What is the extracellular domain of the TCR resemble?
Ig Fab fragment
What binds the chains of the TCR?
disulphide bonds
What is found in the transmembrane region of the TCr?
positively charged amino acids
What is the antigen binding site of hte TCR composed of?
juxtaposed Va and Vb regions
What 2 properties of MHC make it difficult for pathogens to evade the strong immune pressure that MHC presentation exerts?
polygenic- each individual has a set of several MHC class I and II genes which form different molcules with a range of peptide binding sepcificities; polymorphic- multiple variants of each gene within the population as a whole
Which chromosome is the MHC region loacted on in humans?
6
Which chromosome is the mHC region located on in mice?
17
What genes are found in the MHC-II region that aren’t genes for the MHC-II?
genes for LMP-immunoproteasome; TAP; tapasin-antigen presentation; DM-catalyses binding peptide binding to MHC-II; DO-regulatory molecule
What is the difference in stimulation with type 1 IFNs and IFNy?
type I IFNs stimulate MHC-I expression whereas IFNy increase MHC-II expression
What is the MHC haplotype?
the particular combination of MHC alleles foudn on a single chromosome
What disease is caused by defects in Fas?
autoimmune lymphoproliferative syndrome
What is the sequence motif?
the set of anchor residues on a peptide that allows binding to a given isoform of an MHC-I or II
What do the specific anchor residues on peptides bind to on MHC>
peptide binding pockets in the peptide binding groove
What is unusual about HLA-DR?
the alpha chain is essentially invariant and only the beta chain shows significant polymorphism
What was the first clue to antigen presentation on MHC?
inbred animals failing to respond to simple antigens called immune response defects- now known because the processing of the protein did not generate any peptides with a sequence motif for binding to any of the MHC moelcuels expressed by the animal;;;only evidence was genetic, mice of one MHC genotype could respond to a particular antigen whereas mice of a different MHC genotype could not
Why are Ir gene defects common in inbred mice?
mice are homozygous at all their MHC gene loci which limits the range of peptides they can present to T cells
What were the first experiments to describe MHC restriction?
T cells could be activated only by macrophages or B cells that shared MHC alleles with the mouse in which the T cell originated
What experiments carried out by Doherty and Zinkernagel deomnstratewd MHC restriction
?
demonstrated that when mice are infected with virus, T cells kill cells infected with that virus, but not uninfected cells or cells infected with another virus–virus specifc CTLs, also that the CTLs would only kill cells with the same MHC genotype, even if other cells were also infected iwth the same virus
How many amino acids do proteins encoded by polymorphic genes normally differ by and what is the difference in MHC?
usually only by one or a few aa but the allelic variants of MHC differ by upto 20 aa
Give an example of where polymorphism has been shown to be important?
small isolated populations in china and papua new guinea have 60% people carrying the same HLA-A allele, EBV has mutated so that its peptide no longer binds so can no longer be recognised by that alleles restricted T cells
Give an example of where pathogens have selected for MHC alleles?
HLA-B53 allele is very common in west africa- assocaited with recovery from a lethal form of malaria
Why is there a limited number of MHC loci?
each time a MHC molecule is added to the repertoire, all T cells that can respond to self peptide bound to that MHC molecules have to be removed to maintain self tolerance- balance
What is required aside from the alpha and beta chains of the TCR to form a complete and functional receptor?
CD3 complex
Which cells express MHC II?
DCs; B cells; macrophages; thymic epithelium
