T cell receptor structure

Wilson, I.A., Garcia, K.C. T-cell receptor structure and TCR complexes. Curr. Opin. Struct. Biol. 7 839-848, 1997. 

Acuto, 0. and E.L. Reinherz. The human T-cell receptor. Structure and function. N Engl J Med 1985 312(17) 1100-1111. Ortho Multicenter Transplant Study Group. A randomized clinical trial of 0KT3 monoclonal antibody for acute rejection of cadaveric renal transplants. N Engl J Med 1985 313(6) 337-342. 

T-cell receptors (TCR) are heterodimeric transmembrane glycoproteins found exclusively in T cells, with extracellular domains that closely resemble antibody Fab structures. Each of the TCR a and p chains forms half of an extracellular antigen-binding domain, and in addition has one transmembrane... 

To date, there has not been a reported structure determination of a class 11 MHC-peptide-TCR complex. However, T-cell receptors that recognize class... 

Wang, J., et al. Atomic structure of an ap T-cell receptor (TCR) heterodimer in complex with an anti-TCR Fab fragment derived from a mitogenic antibody. EMBO J. 17 10-26, 1988. 

Davis MM, Chien YH, Gascoigne NR et al (1984) A murine T cell receptor gene complex isolation, structure and rearrangement. Immunol. Rev 81 235-258... 

Garcia, K. C. and Teyton, L. (1998), T-cell receptor peptide-MHC interactions biological lessons from structural studies , Curr. Opinion Biotechnol., 4, 338-343. 

Figure 6 The binding of SEB and TSST-1 to the T-ceii receptor. These structures were constructed by using data provided by Entrez s 3-D database and software for moiecuiar modeiing. Primary references for these complexes are SEB plus T-cell receptor and TSST-1 plus T-cell receptor. ...

Ironically, SE or TSST-1 concentrations that cause T-cell proliferation do not always correlate with receptor affinity. For instance, SEE binds HLA-DR with 100-fold lower affinity relative to the very similarly structured SEA however, SEE stimulates T-cell proliferation to equivalent levels as SEA. The dose-response curves for cytokine and chemokine production in vitro by staphylococcal superantigen-stimulated cells are also very similar despite differences in affmity/specificity for major histocompatibility complex class II and T-cell receptor V/3 molecules. Overall, these observations suggest that the biological effects of staphylococcal superantigens are induced at rather low, nonsaturating occupancy rates not readily classified by typical biokinetics. 

Fig. 11.9. Subunit structure of the T cell receptors. The figure shows the different subunits of T cell receptors in a highly simplified representation. The stoichiometry of the subunits in the complete receptor is not clear. The aP chains are also known as the TiaP complex the ye and 8e chains together form the CDS complex. ARAM antigen recognition activation motif...

Some properties of the interactions between antibodies or T-cell receptors and the molecules they bind are unique to the immune system, and a specialized lexicon is used to describe them. Any molecule or pathogen capable of eliciting an immune response is called an antigen. An antigen may be a virus, a bacterial cell wall, or an individual protein or other macromolecule. A complex antigen may be bound by a number of different antibodies. An individual antibody or T-cell receptor binds only a particular molecular structure within the antigen, called its antigenic determinant or epitope. 

F1GURE 5-22 Structure of a human class I MHC protein, (a) This model is derived in part from the known structure of the extracellular portion of the protein (PDB ID 1 DDH). The a chain of MHC is shown in gray the small /3 chain is blue the disulfide bonds are yellow. A bound ligand, a peptide derived from HIV, is shown in red. (b) Top view of the protein, showing a surface contour image of the site where peptides are bound and displayed. The HIV peptide (red) occupies the site. This part of the class I MHC protein interacts with T-cell receptors. 

Note that the mechanism proposed for helper T-cell function requires that T cells have surface receptors that recognize antigen-processing cells, antigen itself, and the appropriate B cell. We will shortly discuss the nature of T-cell receptors, as well as the surface structures they recognize, in a broader context. 

Allison TJ, Garboczi DN. 2002. Structure of y8 T cell receptors and their recognition of nonpeptide antigens. Mol Immunol. 38 1051-1061. 

Li H, Llera A, Mariuzza RA. 1998. Structure function studies of T cell receptor-superantigen interactions. Immunol Rev. 163 177-186. 

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