Structure of T Cell Receptor

1. Alphachain Beta chain Variable region “V” CHO CHO CHO CHO Constant region “C” Hinge “H” Disulfide bridge + Transmembrane region + + Cytoplasmic tail Structure of T Cell Receptor

2. Structure of T Cell Receptor (TCR) • Two polypeptide chains, α and β, of roughly equal length • Both chains consist of a variable (V) and a constant (C) region • α chain V region has a joining (J) segment • β chain V region has both a J and diversity (D) segment

3. Structure of T Cell Receptor(continued) • Hypervariable regions in V contribute to diversity of TCR • TCR recognizes portions of MHC molecule and peptide bound in the groove • Small population of T cells has a TCR comprised of γ and δ chains – γδ TCR specificity differs from αβ TCR

4. Alphachain Beta chain Variable region “V” CHO CHO CHO CHO Constant region “C” Hinge “H” Disulfide bridge + Transmembrane region + + Cytoplasmic tail Structure of T Cell Receptor

5. Properties of Ig and TCR Genes IgTCR Many VDJs, few Cs yes yes VDJ rearrangement yes yes V-pairs form antigen yes yes recognition site Somatic hypermutation yes no

6. Properties of Ig and TCR Proteins IgTCR Transmembrane forms yes yes Secreted forms yes no Isotypes with different yes no functions Valency 2 1

7. CD3 Complex • Group of four proteins associated with TCR • Consists of a γ, a δ, two ε, and two ζ chains • All four proteins are invariant • Functions: 1) synthesized co-ordinately with TCR, required to bring TCR to surface 2) transduces activating signals to T cell when TCR recognizes MHC-peptide

8. TCR α β Recognition CD3 CD3 ε δ γ ε + + - - - - + ζ ζ Signaling CD3 Complex With TCR

9. Accessory Molecules Involved in Cell-Cell Interactions T cell surface molecules that engage with ligand on 2nd cell when TCR recognizes MHC-peptide T CellLigand on 2nd Cell CD4 class II MHC (β2 domain) CD8 class I MHC (α3 domain) LFA-2 LFA-3 LFA-1 ICAM-1, ICA-2 LFA = Leukocyte Function-associated Antigen ICAM = InterCellular Adhesion Molecule

10. Accessory Molecules • All are invariant • Increase adhesion between two engaged cells • Some show increased expression in response to cytokines

11. Costimulatory Molecules • Molecules on T cell and 2nd cell that engage to deliver 2nd signal required for activation of T cell • Most important costimulatory molecules: T cellLigand on 2nd cell CD28 B7-1 (CD80), B7-2 (CD86)

12. peptide T helper lymphocyte Interactions of Th Cell and APC TCR LFA-2 LFA-1 CD28 IL-1 IL-6 TNF-alpha IL-12 IL-15 TNF-beta IFN-gamma GM-CSF IL-4 CD4 Antigen- presenting cell LFA-3 ICAM-1 B7-1/B7-2 (CD80/CD86 Class II MHC

13. peptide Interactions of Tc Cell and Target Cell T cytotoxic lymphocyte TCR LFA-1 LFA-2 CD8 Target cell Class I MHC ICAM-1 LFA-3