Human CTLA-4 Antibody

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. CTLA-4 and CD28 are structurally homologous molecules that are members of the immunoglobulin (Ig) gene superfamily. Both CTLA-4 and CD28 are composed of a single Ig V‑like extracellular domain, a transmembrane domain and an intracellular domain. CTLA-4 and CD28 are both expressed on the cell surface as disulfide-linked homodimers or as monomers. The genes encoding these two molecules are closely linked on human chromosome 2. CTLA-4 was originally identified as a gene that was specifically expressed by cytotoxic T lymphocytes. However, CTLA-4 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, CTLA-4 expression is upregulated rapidly following T cell activation and peaks approximately 24 hours following activation. Although both CTLA-4 and CD28 can bind to the same ligands, CTLA-4 binds to B7-1 and B7-2 with 20-100-fold higher affinity than CD28. The physiological role of CTLA-4 in T cell costimulation is currently being studied. Recombinant human CTLA-4 Fc chimera preparations produced at R&D Systems have been shown to bind both B7-1 and B7-2 with high affinity and to inhibit CD 28 signalling competitively.