T cell activation by a bispecific anti-CD3/anti-major histocompatibility complex class I antibody.
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 or by 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 (less than 20 min) intracellular Ca2+ concentration increases, the bispecific Ab, like antigen-presenting cells plus Ag, produces sustained (greater than 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.
Roosnek
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E
Basel Institute for Immunology, Basel, Switzerland.
Tunnacliffe
A
A
Lanzavecchia
A
A
D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008934:Mitogens; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D003432:Cross-Linking Reagents; D015395:Histocompatibility Antigens Class I; D008934:Mitogens; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D002118:Calcium