Structure and function of programmed death (PD) molecules

Programmed death (PD) molecules belong to the B7 family of co-stimulatory proteins and function in adaptive immunity. PD-1 (CD279) is expressed on lymphocytes and macrophages, and its ligand (PD-L1, CD274) on immune cells and non-hematopoietic cells. Ligation of PD-1 on lymphocytes inhibits T-cell proliferation, cytokine production, and cytolytic function by phosphorylation of immunoreceptor tyrosine-based switch motifs and blockade of T cell receptor signaling. PD-1 and PD-L1 interactions are essential to maintain peripheral immune tolerance and to modulate activation of naïve T cells. Decreased expression results in autoimmunity in mouse models, and increased expression is a key feature of chronic viral infections in humans.