Signal transduction by B7/BB1 expressed on activated T lymphocytes: cross-linking of B7/BB1 induces protein tyrosine phosphorylation and synergizes with signalling through T-cell receptor/CD3.
We report here that B7/BB1 molecules expressed on activated T lymphocytes are involved in signal transduction. Anti-B7/BB1 monoclonal antibody (mAb) enhanced allogeneic proliferative responses against three different B lymphoma lines in a dose-dependent manner, while the same mAb inhibited T-cell response against allogeneic T cells expressing B7/BB1. Induction of B7/BB1 expression on T cells with allogeneic stimulation was confirmed by flow cytometric analysis. With the purified preactivated T cells as responder cells, anti-B7/BB1 mAb costimulated these primed T cells with coimmobilized anti-CD3 mAb. Moreover, cross-linking of B7/BB1 molecules induced protein tyrosine phosphorylation in preactivated T cells with a phosphorylation pattern distinct from those induced by signalling through other T-cell molecules. These results suggest that B7/BB1 molecules function not only as costimulatory ligands expressed on antigen-presenting cells but as receptors on T cells to transduce the costimulatory signals into the cells and may play a role for T-cell-T-cell interactions leading to clonal expansion of activated T lymphocytes. However, the physiological relevance of our finding remains to be explored.
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology*; D051940:B7-2 Antigen; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000276:immunology*; D010766:Phosphorylation; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051940:B7-2 Antigen; D017252:CD3 Complex; C497964:CD86 protein, human; D008562:Membrane Glycoproteins; D014443:Tyrosine