CRYSTAL-STRUCTURE OF THE V-ALPHA DOMAIN OF A T-CELL ANTIGEN RECEPTOR

The crystal structure of the V-alpha domain of a T cell antigen recept or (TCR) was determined at a resolution of 2.2 angstroms. This structu re represents an immunoglobulin topology set different from those prev iously 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) T CR tetramer can be positioned relative to the major histocompatibility complex class II (alpha beta)(2) tetramer with the third hypervariabl e loop of V-alpha over the amino-terminal portion of the antigenic pep tide and the corresponding loop of V-beta over its carboxyl-terminal r esidues. TCR dimerization that is mediated by the alpha chain may cont ribute to the coupling of antigen recognition to signal transduction d uring T cell activation.