A ROLE FOR CD9 MOLECULES IN T-CELL ACTIVATION

Costimulation mediated by the CD28 molecule plays an important role in optimal activation oi T cells. However, CD28-deficient mice call moun t effective T cell-dependent immune responses, suggesting the existenc e of other costimulatory systems. In a search for other costimulatory molecules on T cells, we have developed a monoclonal antibody (mAb) th at call costimulate T cells in the absence of antigen-presenting cells (APC). The molecule recognized by this mAb, 9D3, was found to be expr essed on almost all mature T cells and to be a protein of similar to 2 4 kD molecular mass. By expression cloning, this molecule was identifi ed as CD9. 9D3 (anti-CD9) synergized with suboptimal doses of anti-CD3 mAb in inducing proliferation by virgin T cells. Costimulation was in duced by independent ligation of CD3 and CD9, suggesting that colocali zation of these two molecules is not required for T cell activation. T he costimulation by anti-CD9 was as potent as that by anti-CD28. Moreo ver, anti-CD9 costimulated in a CD28-independent way because anti-CD9 equally costimulated T cells from the CD28-deficient as well as wild-t ype mice. Thus, these results indicate that CD9 serves as a molecule o n T cells that can deliver a potent CD28-independent costimulatory sig nal.