Biology of the T lymphocyte
description
Transcript of Biology of the T lymphocyte
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.