Multivalent structure of an αβT cell receptor

Whether there is one or multiple alpha beta T cell antigen receptor (TCR) recognition modules in a given TCR/ CD3 complex is a long-standing controversy 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 confirmed on the surface of living cells both by fluorescence resonance energy transfer and comodulation assays by using antibodies specific for TCR beta-variable 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 cell activation is thought by many, but not all, to require TCR cross-linking by its antigen/major histocompatibility complex ligand. The implications of a multivalent (alpha beta)(2)TCR/CD3 complex stoichiometry for the ordered docking of specific antigen/major histocompatibility complex, CD4, or CD8 coreceptors and additional TCRs are discussed.