Structural basis of T cell recognition.
Exciting breakthroughs in the last two years have begun to elucidate the structural basis of cellular immune recognition. Crystal structures have been determined for full-length and truncated forms of alpha beta T cell receptor (TCR) heterodimers, both alone and in complex with their peptide-MHC (pMHC) ligands or with anti-TCR antibodies. In addition, a truncated CD8 coreceptor has been visualized with a pMHC. Aided in large part by the substantial body of knowledge accumulated over the last 25 years on antibody structure, a number of general conclusions about TCR structure and its recognition of antigen can already be derived from the relatively few TCR structures that have been determined. Small, but important, variations between TCR and antibody structures bear on their functional differences as well as on their specific antigen recognition requirements. As observed in antibodies, canonical CDR loop structures are already emerging for some of the TCR CDR loops. Highly similar docking orientations of the TCR V alpha domains in the TCR/pMHC complex appear to play a primary role in dictating orientation, but the V beta positions diverge widely. Similar TCR contact positions, but whose exact amino acid content can vary, coupled with relatively poor interface shape complementarity, may explain the flexibility and short half-lives of many TCR interactions with pMHC. Here we summarize the current state of this field, and suggest that the knowledge gap between the three-dimensional structure and the signaling function of the TCR can be bridged through a synthesis of molecular biological and biophysical techniques.
Garcia
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Scripps Research Institute, Department of Molecular Biology, La Jolla, California 92037, USA. garcia@scripps.edu
Teyton
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Wilson
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D000818:Animals; D000906:Antibodies / Q000737:chemistry; D003460:Crystallization; D006801:Humans; D008285:Major Histocompatibility Complex; D008958:Models, Molecular; D010455:Peptides / Q000276:immunology; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry*; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D010455:Peptides; D011948:Receptors, Antigen, T-Cell