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Nivolumab binds to the extracellular portion of human PD-1 (2.6 nM - Scatchard analysis and SPR) - the antibody also binds to cynomolgus PD-1 with a similar affinity (3.9 nM - SPR). The antibody does not bind to other immunoglobulin superfamily proteins such as CD28, CTLA-4, ICOS and BTLA. The epitope of Nivolumab for both human and cynomolgus PD-1 includes the sequences SFVLNWYR-MSPSNQTDKLAAFPEDR (aa 29-53) and SGTYLCGAISLAPKAQIKE (aa 85-103), as shown by mass spectrometry of protease-treated fragments of PD-1 - these residues are thought to additionally be important for liand binding to PD-1. PD-1 is an inhibitory receptor expressed on the surface of T cells. It is able to bind to its ligands PDL-1 and PDL-2 which results in an inhibitory signal leading to decreased T cell proliferation, cytokine protuction and cytotoxic activtiy. PDL-1 is often expressed in human tumors such as melanoma, lung and kidney where it is able to overactivate PD-1 and plays a role in the evasion of cancer cells from the immune system.
Preparation: Recombinant human PD-1-Fc protein consisting of the extracellular domain of PD-1 (amino acids 1-167) and the Fc portion of human IgG1, and Chinese hamster ovary (CHO) cells expressing human PD-1. Nivolumab was generated by grafting the variable regions of PD1.5 onto human kappa and IgG4 constant regions containing an S228P mutation (prevents Fab arm exchange with endogenous IgG4 antibodies).
MA5-51619 is a chimeric antibody. The variable regions from one species have been grafted to the backbone of the other species.
Cell-mediated immune responses are initiated by T lymphocytes that are themselves stimulated by cognate peptides bound to MHC molecules on antig en-presenting cells (APC). T-cell activation is generally self-limited as activated T cells express receptors such as PD-1 (also known as PDCD-1) that mediate inhibitory signals from the APC. PD-1 can bind two different but related ligands, PDL-1 and PDL-2. Upon binding to either of these ligands, signals generated by PD-1 inhibit the activation of the immune response in the absence of "danger signals" such as LPS or other molecules associated with bacteria or other pathogens. Evidence for this is seen in PD1-null mice who exhibit hyperactivated immune systems and autoimmune diseases. Despite its predicted molecular weight, PD-1 often migrates at higher molecular weight in SDS-PAGE.
For Research Use Only. Not for use in diagnostic procedures. Not for resale without express authorization.
Protein Aliases: CD279; CD279; PD-1; hPD1; PD-1; PD1; alternatively spliced; PDCD1; programmed cell death 1 protein; Programmed cell death protein 1; Protein PD-1; Protein PD1; sCD279; soluble CD279; systemic lupus erythematosus susceptibility 2; unnamed protein product
Gene Aliases: AIMTBS; CD279; hPD-1; hPD-l; hSLE1; PD-1; PD1; PDCD1; SLEB2
UniProt ID: (Human) Q15116
Entrez Gene ID: (Cynomolgus monkey) 102123659, (Human) 5133
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