One of the most important events during a T cell response is activation. The discovery and characterization of the co-stimulatory B7/CD28 interaction supports the "two-signal" model for lymphocyte activation. In this model, a lymphocyte requires two distinct signals in order for full activation to occur. The first signal is provided by the interaction of the T cell receptor (TCR) on the lymphoyte with major histocompatibility class (MHC) antigens on the antigen-presenting cell (APC). The second co-stimulatory signal is required to avoid an apoptotic or anergic response by the lymphocyte. The interaction of CD28 on the lymphocyte with B7 proteins on the APC provides this necessary co-stimulatory second signal. If the lymphocyte only receives the first signal (i.e. TCR engagement) from the APC, the lymphocyte becomes apoptotic or anergic, thus unable to respond to antigen.
CD28 and CTLA-4, together with their ligands, B7-1 and B7-2, constitute one of the dominant co-stimulatory pathways that regulate T and B cell responses. CD28 and CTLA-4 are structurally homologous molecules that are members of the immunoglobulin (Ig) gene superfamily. Mouse CD28 is expressed constitutively on virtually 100% of mouse T cells and on developing thymocytes.