The program death 1 (PD-1) receptor CD279 is a 55 kD member of the immunoglobulin superfamily. CD279/PD-1 contains the immunoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic region and plays a key role in peripheral tolerance and autoimmune disease. CD279/PD-1 is expressed predominantly on activated T cells, B cells and myeloid cells. PD-L1 (B7-H1) and PD-L2 (B7-DC) are ligands of CD279/PD-1 and are members of the B7 gene family. Evidence reported to date suggests overlapping functions for these two PD-1 ligands and their constitutive expression on some normal tissues and upregulation on activated antigen-presenting cells. Interaction of CD279:PD-ligands results in inhibition of T cell proliferation and cytokine secretion.