CD80 (B7-1) and CD86 (B7-2) together with their receptors CD28 and CTLA-4 constitute one of the dominant costimulatory pathways that regulate T cell and B cell responses. Although both CTLA-4 and CD28 can bind to the same ligands, CTLA-4 binds to B7-1 and B7-2 with a 20-100 fold higher affinity than CD28 and is involved in the down-regulation of the immune response. B7-1 is expressed on activated B cells, activated T cells and macrophages. B7-2 is constitutively expressed on interdigitating dendritic cells, Langerhans cells, peripheral blood dendritic cells, memory B cells, and germinal center B cells. Additionally, B7-2 is expressed at low levels on monocytes and can be up-regulated through interferon-γ. B7-1 and B7-2 are both members of the immunoglobulin superfamily. It has been observed that both human and mouse B7-1 and B7-2 can bind to either human or mouse CD28 and CTLA-4, suggesting that there are conserved amino acids which form the B7-1/B7-2/CD28/CTLA-4 critical binding sites.