IDENTIFICATION OF AN ALTERNATIVE CTLA-4 LIGAND COSTIMULATORY FOR T-CELL ACTIVATION

Stimulation of T cell proliferation generally requires two signals: Th e first signal is provided by the T cell receptor binding to antigen, and the second signal or costimulus is provided by a different recepto r-ligand interaction. In mouse and human, the CD28-B7 interaction has been identified as a source of costimulatory signals. We have identifi ed a cell surface molecule (GL1) that is distinct from B7 and abundant ly expressed on activated B cells. On activated B cells GL1, rather th an B7, is the predominant ligand for the T cell-activation molecule CT LA-4. GL1 provides a critical signal for T cell-dependent responses in vitro and in vivo.