The three‐dimensional structure of a T‐cell antigen receptor VαVβ heterodimer reveals a novel arrangement of the Vβ domain

The crystal structure of a mouse T‐cell antigen receptor (TCR) Fv fragment complexed to the Fab fragment of a specific anti‐clonotypic antibody has been determined to 2.6 Å resolution. The polypeptide backbone of the TCR Vα domain is very similar to those of other crystallographically determined Vαs, whereas the Vβ structure is so far unique among TCR Vβ domains in that it displays a switch of the c″ strand from the inner to the outer β‐sheet. The β chain variable region of this TCR antigen‐binding site is characterized by a rather elongated third complementarity‐determining region (CDR3β) that packs tightly against the CDR3 loop of the α chain, without leaving any intervening hydrophobic pocket. Thus, the conformation of the CDR loops with the highest potential diversity distinguishes the structure of this TCR antigen‐binding site from those for which crystallographic data are available. On the basis of all these results, we infer that a significant conformational change of the CDR3β loop found in our TCR is required for binding to its cognate peptide‐MHC ligand.