CD28 (human):Fc (human) (rec.)

CD28 and CTLA-4 together with their ligands, CD80 (B7-1) and CD86 (B7-2), constitute one of the dominant costimulatory 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. Both CD28 and CTLA-4 are composed of a single Ig V-like extracellular domain, a transmembrane domain and an intracellular domain. CD28 and CTLA-4 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 and mouse chromosome 1. Mouse CD28 is expressed constitutively on virtually 100% of mouse T cells and on developing thymocytes. Cell surface expression of mouse CD28 is downregulated upon ligation of CD28 in the presence of PMA or PHA. In contrast, CTLA-4 is not expressed constitutively but is upregulated rapidly following T cell activation and CD28 ligation. Cell surface expression of mouse CTLA-4 peaks approx.y 48 hours after activation. 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. CD28/B7 interaction has been shown to prevent apoptosis of activated T cells via the upregulation of bcl-XL. CD28 ligation has also been shown to regulate Th1/Th2 differentiation.