Where can we find MHC1?
All nucleated cells
Where can we find MHC2?
Only found on the surface of some cell types
Structure of MHC1
Alpha 1-3, beta2m + TMD
Structure of MHC2
Alpha1-2, beta1-2 + 2TMDs
What does co-recognition mean?
That a TCR is able to recognize both the MHC molecule and the peptide piece presented by the MHC
What does MHC restriction mean?
?
Why is MHC1 only expressed on nucleated cells?
Because non-nucleated cells lack glycoproteins on the membrane and therefore can’t express this surface protein
What is the function of MHC1?
Presentation of endogenous antigens to cytotoxic T cells
Function of MHC2
Presents exogenous antigens to helper T cells
On what chromosome can we find the genes encoding MHC molecules?
Chromosome 6, on the short arm
Genetic features of MHC molecules
Polygenic: different genes can encode for proteins with overlapping functions (?)
Polymorphic: Different gene variants can encode for different proteins with different functions (?)
Co-dominantly inherited: if allele A is from egg and allele B is from sperm and they both are expressed (both appears on the surface of cells)
What kind of peptides does MHC1 present?
Short, endogenous peptides: 8-9AA (peptide binding side similar to a fixed pocket)
What kind of peptides does the MHC2 present?
Longer, exogenous peptides: 11-25AA
Peptide binding side similar to an open cleft
Process of producing peptide fragment MHC1 + endogenous peptide
Viral DNA/RNA is integrated into nucleus of host cell -> produce viral RNA -> viral proteins -> viral proteins into proteasome (cuts proteins into peptides) in cytosol -> peptides loaded into lumen of RER (MHC1 molecules synthesized here at the same time) -> MHC1 binds peptide -> goes through golgi and finally arrives at the cell surface -> presentation to cytotoxic T cells
Function of TAP (transporter associated with antigen processing)
ATP dependent transporters in the RER membrane that functions to take up the peptides that are more than 8 AA long and have carboxyl ends
Process of producing peptide fragment MHC2 + exogenous peptide
Extracellular self or foreign protein is taken up by endocytosis ->endosomes fuse with lysosomes from golgi -> MHC2 molecules produced in the RER -> vesicles with MHC2 and peptide fragments fuse and are transported by exocytosis to the surface of the cell
Antigen presentation by dendritic cells: where, to who
Carries the pathogen to the lymph node, presents antigen to naive T-cell
Antigen presentation by B-cells and macrophages
Presents antigen to effector T-cell
Proteins encoded by MHC class I genes
HLA-A, -B, -C
Proteins encoded by MHC class II genes
HLA-DP, -DR, -DQ
What chains bind peptide in MHC I?
Alpha chains
Function of invariant chain(Ii)
What is CLIP?
The remaining fragment of Ii cleaved when surroundings are acidic.
Function of HLA-DM?
Helps separating CLIP from MHC II in the lysosome