MHC Flashcards
How do you describe genetically similar organisms or tissues?
Syngeneic
How do you describe genetically dissimilar organisms or tissues of the same species?
Allogeneic
What genes encode antigens?
HLA genes in humans
H2 genes in mice
What is the function of the major histocompatibility complexes?
Essential for recognition of peptide antigens by T cells
Which chromosome are human HLA genes located on?
Chromosome 6
Which chromosome are mice H-2 genes located on?
Chromosome 17
What genes are found in Class III region?
Genes encoding immune regulatory molecules = tumour necrosis factor, C3-5 complement proteins and heat shock proteins
How are MHC alleles expressed?
Codominantly = both are expressed so you get a combined phenotype
Define locus
Physical position on chromosomes where genes are found
Describe allele
Variant of particular polymorphic gene in the population
Define polymorphism
Variation of a specific DNA sequence
Define haplotype
Subset of all alleles on a specific chromosome in the population
Define diplotype
Subset of all genotypes on homologous chromosome pairs in the population
What determines the degree of polymorphism/?
Determined by the number of alleles at each locus
Are MHC genes polymorphic?
Highly
What does an individual carry up to 6 of?
Individual carries up to 6 different Class I MHCs
What is the structure of Class I MHC?
Hetrotrimeric complex = heavy chain, light chain and peptide antigen
What is the Class I heavy chain made of?
3 alpha glycoprotein domains = transmembrane protein
Which domains make up the Class I peptide binding groove?
Alpha 1 & 2
What makes up the light chain?
Beta 2 microglobulin
Where are the genes that encode the b2m of Class I MHC?
The genes are outside the MHC region
How many amino acids long can Class I peptide groove bind?
8-10 amino acids
Why do Class I MHC bind smaller peptide antigens?
Their MHC groove has closed ends and the antigen has to fit wholly into the bowl
Can Class I MHC bind a variety of similar peptides?
Yes, because only specific parts of the antigen are registered
Ony 2-3 amino acids anchor the peptide to the MHC
What activates MHC molecules?
Binding of antigen
What is the structure of Class II MHC?
Heterotrimeric complex = alpha-chain, beta-chain and peptide antigen
Which domains make up the Class II peptide binding groove?
Alpha 1 & Beta 1
Describe Class II MHC binding groove?
Open ended
How many amino acids long can Class II MHC bind?
13-17
Which cells express Class I MHC?
All nucleated cells (not RBCs)
Which cell express Class II MHC?
Only expressed in APC
Name APCs
T cells
B cells
Dendritic cells
Macrophages
Thymic epithelial cells
When can non-APCs express Class II MHCs?
Inflammatory conditions
What role does TCR recognizing MHC-peptide complex play?
T cell development and activation
Why can one person’s T cells not recognize antigens presented on another person’s MHC?
Because people have different MHC types
Where are Class I MHC found?
Mainly in the cytosol of any cell and are presented to cytotoxic T cells leading to cell death
Where are Class II MHC found?
In endocytic vesicles of APCs and are presented to helper T cells
What effects can B cell activation cause?
Secretion of antibodies to eliminate extracellular bacteria/toxins
What effect can macrophage activation cause?
Killing of intra vesicular bacteria and parasites
Where are proteosomes found?
Cytosol
Which part of proteosomes recognize ubiquitin?
19S regulatory cap
Where are TAP1/2 proteins found?
ER membrane
What is the function of TAP1/2 proteins?
Transport viral peptides from cytosol onto Class I MHC molecules in the ER
Where does ATP bind on TAP1/2 proteins?
ABC domain = ATP-binding cassette
How are Class I MHC assembled?
Partly folded alpha chain binds to calnexin until beta 2 microglobulin binds
Released from calnexin and binds chaperone proteins = calreticulin and Erp57
How do Class I MHC present antigens?
Class I MHC bind to TAP via tapasin
Cytosolic proteins are degraded to peptide fragments by proteasome
TAP delivers peptides to Class I MHC = completing its folding
Fully loaded Class I MHC is released from TAP complex and exported
What does the partly folded alpha chain of Class I MHC bind?
Calnexin
What are the two charperone proteins Class II MHC binds?
Calreticulin and Erp57
What allows Class I MHC to bind to TAP?
Tapasin
How are antigens bound to Class II MHC?
Antigens taken up in intracellular vesicle
Early endosomes = endosomal proteases are inactive (neutral pH)
Acidification of vesicles activates proteases = degrade antigen into peptide fragments
Vesicle with peptides fuse with vesicles containing Class II MHC molecules
How does Class II MHC antigen presentation occur?
Invariant chain forms a complex Class II molecules = blocks binding of peptides and misfolded proteins
Invariant chain is cleaved in an acidified endosome = leaving short peptide fragment (CLIP)
Endocytosed antigens are degraded to peptides in endosomes = CLIP still blocks binding
HLA-DM binds to Class II MHC = releasing CLIP
Class II MHC then travels to cell surface
