10- MHC Flashcards
MHC I is found on what kind of cells?
Most nucleated cells
*Not usually present on mammalian red cells, gametes, neurons, or trophoblast cells, this dampens the immune response in sensitive organs
MHC II is found on what type of cells?
B cells, macrophages, and dendritic cells
MHC I presents antigen to which type of T cells? What about MHC II?
MHC I: cytotoxic T cells
MHC II: T-helper cells
What is unique about MHC Class Ia molecules?
Expressed on most nucleated cells, they are the only polymorphic class I molecules- this is important so you can bind to a wide range of pathogens
MHC class Ia molecules are made up of 2 chains. What are they?
A long heavy alpha chain
A short Beta1-microglobulin chain
The antigen binding site of MHC class Ia molecule is formed by which two domains?
Alpha1 and Alpha2 domains
What is the endogenous pathway of MHC I?
MHC I molecules present endogenous peptides which are derived from proteins manufactured by or within the cell.
*These proteins can be normal proteins or viral proteins, if the virus is replicating inside the cell
What are the steps of the endogenous pathway of MHC I
- Ubiquitin binds to the cytoplasmic protein and targets it to proteasome
- proteasome is a cellular organelle that is a hollow cylinder and degrades proteins into short peptides
- Transporter for Antigen Processing (TAP) bind cytotoxic peptides from the proteasome and transport them to the lumen of the ER
- Peptides is trimmed to (aa by the ERAP and then binds to an empty MHC I in the ER
-MHC I plus peptide move to golgi and the transported in exocytic vesicle to cell surface - Antigen-MHC I available for recognition by CD8+ T cell
MHC II are made up of two chains of about similar size. What are they?
Alpha chain
Beta chain
Which two chains form the peptide binding groove on an MHC II molecule?
Alpha 1 and beta 1
List the steps of the exogenous pathway of MHC II
- Uptake of extracellular proteins into vesicular compartments of APC
- Processing of internalized proteins in endosomal/lysosomal vesicles
- biosynthesis and transport of class II MHC molecules to endosomes
- association of processed peptides with class II MHC molecules in vesicles
- expression of peptide-MHC complexes on cell surface
What is MHC restriction?
Only antigen fragments that can bind in the groove of a MHC molecule can trigger an immune response
If antigen does not properly fit MHC, no immune response will be triggered
What determines susceptibility to infectious and autoimmune diseases?
Expression of specific MHC alleles
How many different MHC I and MHC II alleles are there in an average individual?
6 different MHC I and 12 different MHC II
*This seems to be sufficient for a normal immune response
List some examples of MHC-associated resistance or susceptibility to various diseases
1) Association between BoLA-Aw7 and resistance to bovine leukosis (bovine leukemia virus)
2) BoLA-A*16 and resistance to mastitis
3) BoLA DR locus and resistance to Dermatophilus sp.
4) ELA-A9 and susceptibility to equine recurrent uveitis
