Background:

It is widely accepted that 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 expansion and activation. Members of the B7 superfamily of counterreceptors were identified by their ability to interact with costimulatory molecules found on the surface of T cells. Members of the B7 superfamily include B7-1 (CD80), B7-2 (CD86), B7-H1 (PD-L1), B7-H2 (B7RP-1), B7-H3 and PD-L2. B7-1 is expressed on activated B cells, activated T cells, mature dendritic cells and macrophages. T cells express two different receptors capable of binding B7-1, CD28 and CTLA-4. CTLA-4 binds to B7-1 with a 20 - 100 fold higher affinity than CD28. Engagement of CD28 by B7-1 increases T cell proliferation and IL-2 production and enhances the immune response. In contrast, engagement of CTLA-4 is involved in the down-regulation of the immune response. Rat and human B7-1 share 47% amino acid identity.