Lecture 3: Antigen Capture and Presentation Flashcards
Where does antigen presentation to T cells occur?
Spleen and lymph nodes; peripheral lymphoid tissues
What is the immunological synapse?
Interaction between TCR and MHC-peptide complex.
What does the TCR recognize on APCs?
TCR must recognize:
1. MHC polymorphic residues
2. Antigen peptide
MHC classes and their cells
MHC I: all nucleated cells, recognized by CD8+
MHC II: specialized APCs, recognized by CD4+
MHC/HLA gene loci
3 loci each for MHC I and II
I: B, C, A
II: DP, DQ, DR
MHC polymorphism
1 set (haplotype) of HLA inherited from each parent, co-dominantly expressed. Most polymorphic genes in the genome; polymorphisms are localized to peptide binding region
MHC I structure
α1, α2, α3, β2m chains
α1, α2 interact w/ peptide and are therefore the most polymorphic
MHC II structure
α1, α2, β1, β2 chains
α1 + β1 comprise peptide cleft
MHC I processing (endogenous pathway)
- Protein synthesis
- Proteosome processing
- Peptides enter ER chaperoned by TAP
- MHC I-peptide complex assembly in ER (chaperone stabilized)
- Export of MHC-peptide complex to Golgi and then cell surface
Anchor residues
Binding pockets in the floor of MHC peptide binding cleft that directly interact with the peptide; peptides bound to specific MHC share structural features
(TCR) contact residues
AAs facing away from MHC complex that interact with the TCR
MHC II processing (exogenous pathway)
- Endosomal/lysosomal processing of internalized antigens
- Stabilization of MHC II with CLIP in ER
- MHC II-CLIP transport to endosomes
- Antigen peptide-MHC II complex assembly; CLIP leaves
- MHC II-peptide complex export to cell surface
MHC recognition effects
MHC I foreign peptide recognition -> killing of expressing cell
MHC II recognition -> CD4+ activation -> macrophage and B cell activation
