CD152 (CTLA-4) and CD28, together with their ligands B7-1 and B7-2, constitute one of the dominant costimulatory pathways that regulate T and B cell responses. CD152 and CD28 are structurally homologous molecules that are members of the immunoglobulin (Ig) gene superfamily. Both CD152 and CD28 are composed of a single Ig V-like extracellular domain, a transmembrane domain and an intracellular domain. CD152 and CD28 are both expressed on the cell surface as disulfide-linked homodimers or as monomers. CD152 was originally identified as a gene that was specifically expressed by cytotoxic T lymphocytes. However, CD152 transcripts have since been found in both Th1 and Th2, and CD4+ and CD8+ T cell clones. Whereas, CD28 expression is constitutive on the surfaces of 95% of CD4+ T cells and 50% of CD8+ T cells and is down regulated upon T cell activation, CD152 expression is upregulated rapidly following T cell activation and peaks approximately 24 hours following activation. Although both CD152 and CD28 can bind to the same ligands, CD152 binds to B71 and B72 with 20-100-fold higher affinity than CD28.