THE 3-DIMENSIONAL STRUCTURE OF A T-CELL ANTIGEN RECEPTOR V-ALPHA-V-BETA HETERODIMER REVEALS A NOVEL ARRANGEMENT OF THE V-BETA DOMAIN

The crystal structure of a mouse T-cell antigen receptor (TCR) Fv frag ment complexed to the Fab fragment of a specific anti-clonotypic antib ody has been determined to 2.6 Angstrom resolution, The polypeptide ba ckbone bf the TCR V alpha domain is very similar to those of other cry stallographically determined V alpha s, whereas the V beta structure i s so far unique among TCR V beta domains in that it displays a switch of the c '' strand from the inner to the outer beta-sheet. The beta ch ain variable region of this TCR antigen-binding site is characterized by a rather elongated third complementarity-determining region (CDR3 b eta) that packs tightly against the CDR3 loop of the alpha chain, with out leaving any intervening hydrophobic pocket, Thus, the conformation of the CDR loops with the highest potential diversity distinguishes t he structure of this TCR antigen-binding site from those for which cry stallographic data are available. On the basis of all these results, w e infer that a significant conformational change of the CDR3 beta loop found in our TCR is required for binding to its cognate peptide-MHC l igand.