Biology of the T lymphocyte

1. Biology of the T lymphocyte

2. Nature of T cell - overview • T cells have a receptor for Ag on surface (TCR) which share similarities for Ig receptor on B cells; but differs: Ig can interact with Ag directly (even in solution), yet TCR recognize Ag when bound to MHC molecules. • End product of B cell recognition = Ab; T cell recognition • 1) cytokine production • 2) destruction of cells with foreign Ag • Both T & B cells may be activated, proliferate & differentiate to memory cells

3. T cell populations must be able to respond to many foreign antigens, yet NOT bind to self Ag;At least four mechanisms involved; • Basic TCR repertoire determined by number of different germline genes • T cells whose TCR bind to self Ag destroyed within thymus • Surviving T cell populations expanded by positive selection in thymus followed by interaction between TCR and MHC molecules • Peripheral T cell numbers increased by exposure to foreign Ag

4. T cells ab gd CD4+ CD8+ Helper 1 Helper 2 Cytotoxic Regulatory Antigen receptors Accessory molecules Functions * T cell expresses ab+gd- or ab-gd+ but not ab+gd+.

5. CDR1, 2 & 3 NOT T cell specific Figure 9.1 The structure of the T-cell receptor (TCR) complex showing the predominant form of the antigen-binding chains, a and b, and the associated signal transduction complex, CD3 (g, d, and e chains) plus z or h. ITAMs are indicated by the rectangular boxes.

6. CD4 & CD8 • Coreceptor or accessory molecules • T cells: 50 - 60% CD4+, 20 - 25% CD8+ • Two functions • Adhesion molecules : Bind to MHC (CD4 binds to MHC II, CD8 binds to MHC I) --- tighten binding of T cells to APC • Signal transducers : CD4 & CD8 phosphorylated when Ag bound to ab TCR

7. General structure of CD4 & CD8

8. Figure 9.2 The TCR coreceptors and their interaction with MHC molecules. (A) CD4 and (B) CD8.

9. Interactions of TCR & MHC

10. Figure 9.3 The interaction of TCR, MHC, and peptide. The complementarity determining regions (CDRs) of the TCR V regions and peptide bound in the peptide-binding groove of an MHC class I molecule are depicted. [Based on the crystal structure described by K. C. Garcia et al. (1998): Science 279: 1166.]

11. Figure 9.4 Organization of the a, b, and d genes coding for the human T-cell receptor. The organization of the g-gene locus is not shown because of its complexity.

12. Germ-line organization of the mouse TCR

14. Example of gene rearrangements for ab T-cell receptor

16. Figure 9.5 The developmental pathways of T cells in the thymus. Genes coding for the a, b, g, and d chains of the T-cell receptor are designated as a0 etc. if unrearranged and a+ if rearranged.

19. Figure 9.6 Positive and negative selection of ab+CD4+CD8+ T cells in the thymus.