4. Antigen Processing and Presentation Flashcards
What is MHC restriction?
- T cell co-recognition of a foreign peptide/ self MHC molecule
> particular MHC allele restricts ability of T cells to recognize antigens
Cytosolic pathogens bind to what MHC class?
MHC class I
- present antigen to effector CD8 T cells
Intravesicular pathogens bind to what MHC class?
MHC class II
- present antigen to effector CD4 T cells
Extracellular pathogens bind to what MHC class?
MHC class II
- present antigen to effector CD4 T cells
> activation of B cells to secrete Ig to eliminate extracellular pathogens
How can extracellular antigens be displayed on MHC I?
(normally on MHC class II)
- cross-presentation of extracellular antigens on MHC class I molecules by DCs
> translocation of proteins from phagolysosome > cytosol for degradation by proteasome > resultant peptides passed into ER where they load onto MHC I
> direct transport of antigens from phagolysosome > vesicular loading compartment where they load onto MHC I (no passage through cytosol)
How can extracellular antigens be cross-presented on MHC class I molecules by DCs?
- translocation of proteins from phagolysosome > cytosol for degradation by proteasome > resultant peptides passed into ER where they load onto MHC I
- direct transport of antigens from phagolysosome > vesicular loading compartment where they load onto MHC I (no passage through cytosol)
How can cytosolic antigens be displayed on MHC class II?
(normally on MHC class I)
- autophagy pathways can deliver cytosolic antigens for presentation by MHC class II molecules
- portions of cytoplasm are taken into autophagosomes
> specialized vesicles fused with endocytic vesicles/ lysosomes - contents catabolized > peptides can be bound to MHC II
What cells express MHC class I molecules?
- all nucleated cells
- not RBCs (unnucleated)
- most highly expressed in hematopoietic cells
What kind of protein is MHC molecule?
- member of immunoglobulin superfamily
> has immunoglobulin domains
Where is the peptide-binding groove formed in both MHC class I/ MHC class II molecules?
- by the membrane-distal domains
- MHC class I > α1/ α2 domains
- MHC class II > α1/ β1 domains
Where is the immunoglobulin domain structure in MHC class I/ MHC class II molecules?
- in the membrane-proximal domains
How are peptides bound differently in MHC class I/ II?
- MHC class I > peptide bound in elongated conformation/ both ends tightly bound at either end of the cleft (closed at both ends)
- MHC class II > peptide bound in elongated conformation/ ends of peptide not tightly bound > peptide extends beyond cleft (open at both ends)
What are the structural characteristics of MHC class I?
- present antigens to CD8+ T cells
- composed of 4 domains: α1/ α2/ α3/ β2 microglobulin
- α3/ β2 microglobulin > proximal/ fold similar to Igs
- α1/ α2 domains > antigen binding groove/ highly polymorphic
What are the structural characteristics of MHC class II?
- present primarily on APCs > present antigens to CD4+ T cells
- composed of 2 separate chains: α/ β
- each MHC II chain is folded into 2 domains > α1 and α2/ β1 and β2
- α1/ β1 domains form antigen binding groove
- β chain is polymorphic (especially β1 domain)
How do MHC class I molecules interact with peptides?
> bound by their ends
- series of hydrogen bonds/ ionic interactions at each end
- AA that form these bonds are common to all MHC class I molecules