Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the CD274 gene.[5]
Programmed death-ligand 1 (PD-L1) is a 40kDa type 1 transmembrane protein that has been speculated to play a major role in suppressing the adaptive arm of immune systems during particular events such as pregnancy, tissue allografts, autoimmune disease and other disease states such as hepatitis. Normally the adaptive immune system reacts to antigens that are associated with immune system activation by exogenous or endogenous danger signals. In turn, clonal expansion of antigen-specific CD8+ T cells and/or CD4+ helper cells is propagated. The binding of PD-L1 to the inhibitory checkpoint molecule PD-1 transmits an inhibitory signal based on interaction with phosphatases (SHP-1 or SHP-2) via Immunoreceptor Tyrosine-Based Switch Motif (ITSM).[6] This reduces the proliferation of antigen-specific T-cells in lymph nodes, while simultaneously reducing apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells) – further mediated by a lower regulation of the gene Bcl-2.[citation needed]. PD-L1 is expressed on both hematopoietic and nonhematopoietic cells in tissues. However, the exact roles of PD-L1 on hematopoietic versus nonhematopoietic cells in modulating immune responses are unclear.[7]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000120217 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000016496 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: CD274 CD274 molecule".
- ^ Chemnitz JM, Parry RV, Nichols KE, June CH, Riley JL (July 2004). "SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation". Journal of Immunology. 173 (2): 945–954. doi:10.4049/jimmunol.173.2.945. PMID 15240681.
- ^ Mueller SN, Vanguri VK, Ha SJ, West EE, Keir ME, Glickman JN, et al. (July 2010). "PD-L1 has distinct functions in hematopoietic and nonhematopoietic cells in regulating T cell responses during chronic infection in mice". The Journal of Clinical Investigation. 120 (7): 2508–2515. doi:10.1172/JCI40040. PMC 2898584. PMID 20551512.