The crystal structure of the V-alpha domain of a T cell antigen receptor (TCR) was determined at a resolution of 2.2 angstroms. This structure represents an immunoglobulin topology set different from those previously described. A switch in a polypeptide strand from one beta sheet to the other enables a pair of V-alpha homodimers to pack together to form a tetramer, such that the homodimers are parallel to each other and all hypervariable loops face in one direction. On the basis of the observed mode of V-alpha association, a model of an (alpha beta)(2) TCR tetramer can be positioned relative to the major histocompatibility complex class II (alpha beta)(2) tetramer with the third hypervariable loop of V-alpha over the amino-terminal portion of the antigenic peptide and the corresponding loop of V-beta over its carboxyl-terminal residues. TCR dimerization that is mediated by the alpha chain may contribute to the coupling of antigen recognition to signal transduction during T cell activation.