T cell activation by a bispecific anti-CD3/anti-major histocompatibility complex class I antibody

Abstract

A bispecific anti‐CD3/anti‐major histocompatibility complex (MHC) class I antibody (Ab) that is able to activate human T cells in the absence of a second signal has been used to compare activation by this Ab to signaling by anti‐CD3 Ab orby antigen (Ag). We have studied early, intermediate and late events that occur after triggering of a tetanus toxoid‐specific T cell clone. While bivalent anti‐CD3 Ab induce transient ( 2 h) elevated intracellular Ca²⁺ concentration. In addition, while the anti‐CD3 Ab only induces low levels of c‐myc mRNA lasting less than 3 h, the bispecific Ab induces high levels which are maintained for at least 8 h after triggering. Late events, such as interleukin 2 receptor expression and proliferation, occurring more than 20 h after activation, were seen only when T cells were stimulated by bispecific Ab or by antigen‐presenting cell and Ag. Cells activated by linking T cell receptor(TcR)/CD3 to MHC class I antigens could not be activated by cross‐linking the MHC and TcR/CD3 structures separately. Therefore, we propose that the bispecific Ab functions by modifying the membrane dynamics of the TcR/CD3 complex, rather than by the generation of a second signal through class I antigens.