Back to your search result

Description

Programmed cell death protein 1 (UniProt: Q15116, also known as Protein PD-1, hPD-1, CD279) is encoded by the PDCD1 (also known as PD1) gene (Gene ID: 5133) in human. PD-1 is a monomeric inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. PD-1 is synthesized with a signal peptide (aa 1-20), which is subsequently cleaved off. The mature form contains an extracellular domain (aa 24-170), a transmembrane domain (aa 171-191), and a cytoplasmic domain (aa 192-288). PD-1 also contains a single N-terminal immunoglobulin variable region (IgV) like domain. PD-1 and its ligands, PD-L1 and PD-L2 play a key role in the maintenance of peripheral tolerance, a process by which the quiescence of autoreactive mature T cells is maintained. However, tumors and pathogens that cause chronic infections can exploit this pathway to escape T-cell mediated tumor-specific and pathogen-specific immunity. The effector functions of T-cells expressing PD-1 can be downregulated by PD-L1 or PD-L2 expressed by the tumor cells. PD-1 lacks SH2- or SH3-binding motifs on its cytoplasmic tail, but contains the N-terminal sequence VDYGEL that forms an immunoreceptor tyrosine-based inhibition motif (V/I/LxYxxL), which recruits SH2 domain-containing phosphatases. The cytoplasmic tail also contains the C-terminal sequence TEYATI, which forms an immunoreceptor tyrosine-based switch motif (TxYxxL). PD-1 ligation is reported to inhibit the activation of T-cell receptor proximal kinases, which results in attenuation of Lck-mediated phosphorylation of ZAP-70 and initiation of downstream events. PD-1 is also reported to impair the activation of the MEK-ERK MAP kinase pathway by inhibiting activation of PLC- 1 and Ras. (Ref.: Boussiotis, VA (2016). N. Engl. J. Med. 375, 1767-1778).