1. Principles of Immunology T Cell Receptors 3/9/06 “Education is a better safeguard of liberty than a standing army.” Edward Everett

2. Word/Terms List  CD3  CDR  Heterodimer  Homodimer  ITAM  TCR Complex

3. Study of TCRs  Early studies of Ag response B cells/Ab  TCRs as an Ig/ IgT

4. Comparing BCRs vs. TCRs  BCRs Soluble Ags Non MHC restricted  TCRs Membrane bound Ags MHC restricted (self)  Both are Ag specific

6. TCR and BCR Structural Comparison  BCR “Dimer of dimers” (two heterodimers)  Two dimers of one heavy/one light  Varying number of domains. For IgG 4 and 2 ;IgM 5 and 2  Constant and variable domains Bivalent for Ag binding  CDRs in Fab

7. TCR and BCR Structural Comparison  TCR Heterodimer  One alpha/one beta  Two domains each  Constant and variable domains Monovalent for Ag Hypervariable regions in V domains

9. TCR Complex  Includes the TCR plus CD3  CD3 Contains six chains  One homodimer  Two different heterodimers Has many ITAMs  Function?  Significance? Essential for TCR expression and post Ag recognition signal transduction Intra membrane oppositely charged residues

12. Two Types of TCRs  Predominantly alpha/beta  Also see gamma/delta Gamma/delta TCR cells are less discriminating Respond to phospholipid Ags May be “first responders”

14. TCR Genetic Diversity  TCR gene expression Seen in T cells only  Alpha chain encoded by V and J segments (~ to Ig light chains)  Beta chain encoded by V, D and J segments (~ to Ig heavy chains)  Combinatorial joining occurs resulting in at least 3 million combinations  No somatic mutation contributing to diversity

16. TCR Accessory Molecules  Act as co-receptors CD4  Monomer; four domains CD8  Heterodimer; one domain each CD2  Each accessory molecule reacts with a ligand on the APC or target cell

20. TCR Binding vs. BCR Binding  TCR binding with Ag Less specific than BCR Less tightly bound But more adhesion molecules Greater number of ITAMs