L4: Major Histocompatability Complex Flashcards
What is the MHC?
a large cluster of genes encoding specialized glycoproteins. Has many functions but for us it has a role in antigen presentation to T cells.
How is antigen recognition by T cells different from antibody:antigen recognition?
T cells ONLY recognize peptides bound to MHC molecules
How are class I and class II MHC different?
???
How many different peptides can each MHC bind to?
many different peptides
A peptide is 15 AA’s long, can it bind to Class I or Class II MHC, or both?
It can only bind to Class II because Class I MHC will only bind to peptides betwen 8-10 AA’s in length because they are closed at the ends whereas Class II are open.
What is binding of MHC class I molecules stabilized by?
regions in the basement of the cleft that induce fit.
AND
Contacts betweeen A-terminal ends and C-terminal ends of the peptice and invariant sites found at the ends of the binding groove. (this is only true of Class I)
Which class of MHC follows the hotdog in a bun model of binding?
Class II. It has open ends, allowing it to bind to very long peptide chains.
How is peptide binding stabilized in class II MHC molecules?
by contacts between the peptide backbone and conserved residues that line the binding groove
Which class MHC molecule has more restricted binding?
Class I. It is restricted to smaller peptides
What is the TAP transporter complex?
After proteosomes break proteins into peptide fragments, the TAP transporter moves some of those fragments from the cytosol to the ER lumen, and ultimately loaded onto Class I MHC molecules.
Can an MHC class I molecule without an peptide bound to it move to the golgi then the cytoplasm?
No. It will degrade rather rapidly in the ER if it doesn’t bind to a peptide
What type of MHC is recognized by CD8 T cells?
Class I MHC.
What types of cells synthesize class II MHC?
antigen presenting cells and thymus cells
What types of cells synthesize class I MHC?
almost all nucleated cells.
What prevents proteosomal derived peptide chains from binding to MHC class II molecules?
The invariant chain, which is bound to the class II MHC until it is in a vesicle, at which point it breaks down but leaves CLIP fragment in the binding groove. Once the vesicle fuses with an antigen filled endosome, HLA-DM removes CLIP fragment and peptides bind to the groove and are presented on cell surface.
What type of MHC do CD4 T cells bind to?
Class II.
What type of peptides are usually found in class I MHC: intracellular or extracellular?
Intracellular. Via proteosomal degradation and ER.
What is the enzyme that allows release of the CLIP fragment in class II MHC?
HLA-DM
What type of peptides are usually found in class II MHC: intracellular or extracellular?
extracellular pathogens. Invariant chain prevents intracellular pathway from occurring.
What type of peptide is usually bound to MHC: self or pathogen?
Usually only self molecules, except in times of infection.
What type of tissue is low in MHC class I molecules?
Neural tissue. Really don’t want CD8 T cells attacking infected neural cells.
Which type of pathogens are Ab-mediated immune responses best for: intracellular or extracellular? What type of T cell helps? What class MHC?
Ab-mediated immune responses are best for clearance of extracellular pathogens, which are bound to Class II MHC, which illicit responses from CD4 T cells.
Which type of pathogens are CD8 T cell-mediated immune responses best for: intracellular or extracellular? What class MHC?
Intracellular pathogens are best cleared by CD8 T-cell mediated responses, which use Class I MHC
Define Polygeny.
Existence in the genome of several different genetic loci encoding structurally similar proteins of identical functions
Define polymorphism.
existence of two or more forms of a given gene within the population
What are the two most polymorphic sets of genes in the body? Why?
MHC class I and II. Each person inherits 3 MHC class I genes on each chromosome and at least 3 class II genes on each chromosome.
What are the genes for Class I MHC?
HLA-A, HLA-B, HLA-C
What are the genes for Class II MHC? In which of these can you inherit multiple beta chains? Is there an advantage to this?
HLA-DP, HLA- DQ, HLA-DR.
HLA-DR you can inherit 1 or 2 beta chains.
Having more is a huge advantage because you can create more polymorphisms of the MHC molecule so you can present a wider variety of antigens.
Why don’t you see much variability in binding of MHC class I molecules with various alpha chains?
There is little variability between the HLA-A genes and few polymorphisms.
If you inherit homozygously at all positions of the MHC class I and class II molecules, how many different types of MHC can you make of each?
only 3 different class I and 3 class II. This is the minimum possible.
If a person inherits heterozygously for all MHC class I genes, how many different MHC class I molecules can they produce? What is the max if this happened for class II?
6 for Class I all hetero
48 for Class II all hetero
