T cells require a signal induced by the engagement of the T cell receptor and a costimulatory signal(s) through distinct T cell surface molecules for optimal T cell activation and tolerance. CD273 (PD-L2) is one of two ligands for programmed death-1 (PD-1; CD279), a member of the CD28 family of immunoreceptors. The other identified ligand is PD-L1. CD273 is broadly expressed and also up regulated in a variety of tumor cell lines. On previously activated T cells, CD273 interaction with PD-1 inhibits TCR mediated proliferation and cytokine production, suggesting an inhibitory role in regulating immune responses. CD273 has a costimulatory function on resting T cells activated with suboptimal TCR signals.