Biology of the T lymphocyteBiology of the T lymphocyte

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

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

T cells

CD4+ CD8+

Helper 1 Helper 2 Cytotoxic Regulatory

Antigen receptors

Accessorymolecules

Functions

* T cell expresses or but not+.

Figure 9.1The structure of the T-cell receptor (TCR) complex showing the predominant form of the antigen-binding chains, and , and the associated signal transduction complex, CD3 (, , and chains) plus or . ITAMs are indicated by the rectangular boxes.

NOT T cell specific

CDR1, 2 & 3

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 TCR

General structure of CD4 & CD8

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

Interactions of TCR & MHC

Figure 9.3The 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.]

Figure 9.4Organization of the , , and genes coding for the human T-cell receptor. The

organization of the -gene locus is not shown because of its complexity.

Germ-line organization of the mouse TCR

Example of gene rearrangements for T-cell receptor

Figure 9.5The developmental pathways of T cells in the thymus. Genes coding for the , , , and chains of the T-cell receptor are designated as 0 etc. if unrearranged and + if rearranged.

Figure 9.6Positive and negative selection of +CD4+

CD8+ T cells in the thymus.