4. Antigen Presentation And Processing Flashcards
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)
- Binding to MHC II in RER to prevent self peptide from binding
- Targets MHC II for lysosome
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
Which chains binds the peptide in MHC II?
Alpha and beta chains
CD1 function
Has a structure similar to MHC I -> can present lipid Ag fragments
