T CELL DEVELOPMENT MHC 1 and 2

T CELL DEVELOPMENT MHC 1 and 2

1. CLASS 1 MHC

   • Recognized by CD8 T Cells
     • CD8 co-receptor binds MHC I a3 domain, which has a species- T Cell Receptor 8-10 AA CD8 specific constant amino acid sequence
   • Heterodimer of membrane bound alpha chain and non-covalently associated Beta2-microglobulin
     • Genes are highly polymorphic
     • ALPHA CHAIN DOMAINS
       • Alpha 1
         • Alpha 2
           • Alpha 3
     • Proteins are expressed on ALL nucleated cells
     • Beta2-microglublin is absolutely necessary for binding to occur
   • Antigen binds MHC I a1 and a2 domains
     • Variability is maximized
     • MHC I can hold an 8-10 amino acid peptide because the "cleft" is closed
     • a1 and a2 domains also bind TCR.
   • Class 1 Genes
     • Youu'll receive HLA from both mom and dad EVERYTHING is expressed (6) CoDominance is seen
       • MOM Gives: HLA-A - HLA-B - HLA-C DAD Gives: HLA-A - HLA-B - HLA-C
   • Peptides which bind to Class I ARE anchored by their amino and carboxyl termini.

2. Class 2 MHC

   • Recognized by CD4 T cells
     • a2 binds CD4 co-receptor
   • a1 and b1 domains also bind TCR. The membrane-bound a2 and b2 domains are invariant
   • MHC II peptide-binding site binds longer peptides than MHC I (13-50 residues) .
   • Class 2 Genes
     • HLA-DP (alpha and beta) HLA-DQ (alpha and beta) HLA-DR (alpha and beta)
   • Peptides which bind to Class II are not anchored by their amino and carboxyl termini.
     • Class II-binding peptides have 2 anchor residues that must be of certain types to bind a particular allele
   • MHC II proteins are found on: B cells, Dendritic Cells, Macrophages, and Thymic epithelial cells (a non AG presenting cell)

3. B CELLS and T CELLS

   • SIMILARITIES 1. Beta chain structure is similar to heavy chain structure (VDJ) and Alpha chain structure is similar to light chain structure (VJ)  2. Both B and T cells have a variable and constant region. 
   • DIFFERENCES 1. T Cell Receptors are ALWAYS membrane bound. whereas B cells can be secreted OR membrane bound  2. T cells have ONE binding site and B cells have TWO antigen binding sites

4. Importance of MHC Presentation

   • To fight certain endogenous and certain exogenous pathogens
     • Endogenous Pathogens: reproduce in host cell cytosol (ALL viruses and some intracellular bacteria/ protozoan parasites) AKA Cytoplasmic Pathogens
       • Cytotoxic T cells (CD8 T cells) must be activated
     • Exogenous Pathogens: AGs are often phagocytksed and destroyed by lysosomal enzymes
       • Can be TRULY extracellular of Intravesicular
       • Utilizes CD4 T cells "Helper T Cells"