MHC Flashcards
What do T-cell receptors bind?
They do NOT bind antigens directly
They bind processed peptides on the major histocompatibility complex (MHC)
The final ligand is a peptide-MHC ligand
What are the two types of peptide-MHC ligands?
- Peptide-MHC 1 - interacts with Cytotoxic T cells (CD8+)
2. Peptide-MHC 2 - interacts with helper T cells (CD4+)
What are the functions of four general type of T-helper cells?
Th1 - inflammatory cytokine production - IFN-y, TNFa
Th2 - signal B cells for class switching
Th17- inflammatory cytokine production - IL-17
ThF - signal for B cells to expand in lymphoid follicles
How are T cells and MHC involved in transplant rejection?
T cells will interact with foreign MHC molecules present on transplanted tissue
Why is MHC polymorphism good and bad?
Bad because it makes tissue transplant difficult
Good because there is more ‘self-ness’ to each person which helps the population be resistant to many infectious agents
What genes control MHC class 1 production? What part of the receptor is polymorphic vs not?
HLA-A, HLA-B, and HLA-C which are all highly polymorphic. These code the alpha chain which has three domains.
The beta2 microglobulin is coded by non-MHC loci, and is not polymorphic. It serves to stabilize the MHC Class 1 receptor so it can present peptide effectively.
What genes control MHC class 2 production? What part of the receptor is polymorphic vs not?
HLA-DP, HLA-DQ, HLA-DR which are polymorphic. Each locus has A and B which code for alpha and beta chains which contribute equally to the MHC Class 2 receptor. Thus, there are 6 class 2 genes on each chromosome.
How many HLA genes does each person have? What is their expression?
12, 6 from one parent and 6 from the other, which can all be different.
These are all co-dominantly expressed
What does HLA-B*17 mean?
HLA-B gene for that person is allele group 17. Other numbers indicate specific protein substitutions / changes.
How large is the peptide-binding groove of MHC Class I? Which alpha domain interacts with B2 microglobulin, and what else does it touch?
8-11 amino acids
Alpha3 interacts with the B2 protein, and also the CD8 molecule on T cells.
What are anchor residues? How many on MHC Class 1?
2-3 positions of the processed peptide on MHC are critical in that they must have amino acids of a particular class in order to fit (i.e. positive charge, negative charge, hydrophobic, aromatic).
What is the CD4 binding site on MHC Class 2?
Beta-2 domain
How large is the peptide-binding groove of MHC Class 2? How many anchor residues?
13-30 amino acids, with 2-4 anchor residues
What cells is MHC class 1 expressed on?
All nucleated cells
What cells is MHC class 2 expressed on?
APCs, DCs, B cells, and thymic epithelial cells
What cytokine increases antigen expression activities to induce MHC Class 2 expression?
Interferon gamma
What is the pathway for antigen presentation on MHC Class 1? What proteins are involved in translocation to the ER?
Proteins are degraded by the proteasome (can be self or non-self). TAP-1 and TAP-2 transport proteins to the ER, where fragments become associated with the newly formed MHC Class 1. These peptides will be presented on the surface of the cell.
What types of cells are targeted by MHC Class 1?
Those with peptides from intracellular pathogens / parasites whose proteins would’ve been broken down by the proteasome
What types of antigens are targeted by MHC Class 2?
Foreign peptides which have been phagocytosed by an APC, serves to generate T helper cells.
What is the mechanism of MHC Class 2 presentation?
MHC Class 2 is assembled in ER and stabilized by CD74.
CD74 degrades to CLIP after vesicle ships from Golgi.
Phagocytosed and acid-digested vesicle fuses with MHC vesicle, and HLA-DM mediates CLIP removal.
The immunodominant protein fragment will bind
Can antigens bind to MHC at cell surface? Why might this not happen?
Yes they can, but it is rare since naked MHC molecules are unstable and cannot be transported to the cell surface
What is cross-processing?
Pathways can overlap, and APCs can also express exogenous proteins on MHC Class 1
