Engagement of CD28 by B7-1 (CD80) or B7-2 (CD86) in the presence of antigen promotes T cell proliferation, cytokine production, differentiation of effector T cells, and the induction of Bcl-x, a promoter of T cell survival. Conversely, engagement of CTLA4 by B7-1 or B7-2 may inhibit proliferation and IL-2 production. Pdcd-1L1 (programmed cell death ligand-1), also known as B7-H1 or PD-L1, is 290 amino acid type I transmembrane protein which is 20% and 15% identical to B7-1 and B7-2, respectively. Pdcd-1L2 has immunoglobulin V-like and C-like domains and a 30 amino acid cytoplasmic tail. It does not bind CD28, cytotoxic T-lymphocyte A4 or ICOS (inducible co-stimulator). IL-2, although produced in small amounts, is required for the effect of Pdcd-1L1 co-stimulation. The gene which encodes Pdcd-1L1 maps to human chromosome 9p24. Pdcd-1L2 (programmed cell death ligand-2) is a 73 amino acid protein which contains a signal sequence, IgV- and IgC-like domains, a transmembrane region and a cytoplasmic region. The gene which encodes Pdcd-1L2 maps to human chromosome 9p24.2. The constitutive expression of Pdcd-1L1 and Pdcd-1L2 on paren-chymal cells of heart, lung and kidney suggests that the Pdcd-1-Pdcd-L system could provide unique negative signaling to help prevent autoimmune disease.
