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Description

Programmed cell death 1 ligand 1 (UniProt: Q9EP73, also known as PD-L1, PDCD1 ligand 1, Programmed death ligand 1, B7 homolog 1, B7-H1, CD274) is encoded by the CD274 (also known as B7h1, Pdcd1l1, Pdcd1lg1, Pdl1) gene (Gene ID: 60533) in murine species. PD-1 and PD-1 ligands 1 and 2 (PD-L1 and PD-L2) are B7:CD28 family members that regulate T cell activation and peripheral tolerance. PD-L1 is initially produced with signal peptide (aa: 1-18) sequence, the removal of which yields the mature protein with a large extracellular (aa: 19-238) region that contains an Ig-like V-type domain (aa: 19-127) and an Ig-like C2-type domain (aa: 133-225), followed by a transmembrane domain (aa: 239-259) and a cytoplasmic tail (aa: 260-290). When engaged together with the TCR, the interaction of PD-1 with its ligands delivers an inhibitory signal to T cell proliferation and cytokine production. While PD-L1 is broadly expressed in hematopoietic and non-hematopoietic cells, PD-L2 expression is highly restricted to antigen presenting cells (APCs), including dendritic cells (DCs) and macrophages. The PD-1 pathway plays a key role in the progressive loss of effector T cell responses during chronic HIV infection. Tumor-associated PD-L1 is reported to facilitate apoptosis of activated T cells and stimulate IL-10 production in T cells to mediate immune suppression. These effects can be blocked by some monoclonal PD-L1 antibodies and T cell function can be restored. (Ref.: Chen, L., and Han, X (2015). J. Clin. Invest. 125(9): 3384-3391).