T cell activation requires two signals from antigen-presenting cells (APCs). The antigen-specific major histocompatibility complex (MHC) signal is mediated via the interaction between the antigen-MHC complex localized on the surface of APCs and the T cell receptor localized on the surface of T cells. The non-antigen specific, co-stimulatory signal occurs via the interactions between stimulatory ligands on the APC surface and T cell surface receptors. Several TNF superfamily members mediate T cell co-stimulation. These include 4-1BB, CD27, CD30, CD40, GITR, HVEM, DR3, and OX40 and their respective ligands, as well as TACI or BAFF R activation by BAFF, TNF RII activation by TNF-alpha, and activation of RELT by an unknown ligand.