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 BCLX, a promoter of T-cell survival. Engagement of CTLA4 by B7-1 or B7-2, on the other hand, may inhibit proliferation and interleukin-2 (IL-2) production. PD-L1 is 290-amino acid type I transmembrane protein, which is 20% and 15% identical to B7-1 and B7-2, respectively, has immunoglobulin V-like and C-like domains and a 30-amino acid cytoplasmic tail. PD-L1 does not bind CD28, cytotoxic T-lymphocyte A4 or ICOS (inducible co-stimulator). IL-2, althoµgh produced in small amounts, is required for the effect of PD-L1 co-stimulation. PD-L2 protein contains a signal sequence, IgV- and IgC-like domains, a transmembrane region and a cytoplasmic region. The constitutive expression of PD-L1 and PD-L2 on parenchymal cells of heart, lung and kidney sµggests that the PD-1-PD-L system could provide unique negative signaling to help prevent autoimmune diseases.
