Specificity of T cell receptors

The functional specificities of T cells is attributed mainly to the TCRs because the recognition of the antigenic peptides and MHC polypeptides ultimately depends on the final conformation and folding of the «(3 TCR heterodimer. Thus, a direct and simple structure-functional relationship between T cell specificity and primary TCRa and TCR (3 chain structure would be unexpected in most cases. Surprisingly, however, there are many examples in which a direct relationship exists between the specificity of the antigen and the primary sequence of the TCR. This correlation of structure and function breaks down into two categories: one including standard antigenic peptide-MHC complexes, and the other including 'superantigens', a class of antigens covering bacterial products (e.g. enterotoxins), minor lympho-cyte-stimulating antigens Mis (e.g. endogenous retroviral products) and certain MHC products (e.g. l-E).

The most striking examples for the first category are the use of particular TCR-V„ segments to recognize certain cytochrome c peptides in association with I-E products, and the use of specific TCR-VrJ„, TCR-VpJp combinations to recognize a peptide from the myelin basic protein in association with I-A" products. For superantigens, the correlation is often to a particular V gene (especially TCR-V(< segments), with little structural contribution by the D and J gene segments or junctional sequences. It is likely that the conformation of these V gene segments possesses intrinsic affinity for these superantigens.

At this time, it is not known precisely how a(3 TCR heterodimers interact with their ligands (antigenic peptide-MHC product complexes). One hypothesis suggests that the V gene segments may recognize the MHC polypeptides while the V-D-f junctions make contact with the antigenic peptides. An understanding of the mechanism of this dual recognition may be gained when the three-dimensional conformational interactions between the a(3TCR heterodimers and the peptide-MHC complex are defined.

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