Multivalent structure of an alpha beta T cell receptor

Whether there is one or multiple alpha beta T cell antigen receptor (TCR) r ecognition modules in a given TCR/ CD3 complex is a long-standing controver sy in immunology. We show that T cells from transgenic mice that coexpress comparable amounts of two distinct TCR beta chains incorporate at least two alpha beta TCRs in a single TCR/CD3 complex. Evidence for bispecific alpha beta TCRs was obtained by immunoprecipitation and immunoblotting and confi rmed on the surface of living cells both by fluorescence resonance energy t ransfer and comodulation assays by using antibodies specific for TCR beta-v ariable regions. Such (alpha beta)(2)TCR/CD3 or higher-order complexes were evident in T cells studied either ex vivo or after expansion in vitro. T c ell activation is thought by many, but not all, to require TCR cross-linkin g by its antigen/major histocompatibility complex ligand. The implications of a multivalent (alpha beta)(2)TCR/CD3 complex stoichiometry for the order ed docking of specific antigen/major histocompatibility complex, CD4, or CD 8 coreceptors and additional TCRs are discussed.