PD1 Recombinant Rabbit Monoclonal Antibody [SJ01-91]

Function

Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self. Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2. Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation. Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta. The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival. The interaction with CD274/PDCD1L1 inhibits cytotoxic T lymphocytes (CTLs) effector function. The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy. The interaction with nivolumab is not dependent on glycosylation and depends on a loop at the N-terminus (N-terminal loop, corresponding to residues 25-34). Targeting the interaction between PDCD1 and CD274/PDCD1L1 with pembrolizumab and nivolumab antibodies has demonstrated great promise as a strategy for controlling and eradicating cancer. Pembrolizumab and nivolumab are used for treatment of patients with advanced melanoma. These antibodies are also effective against other cancers, such as non-small cell lung cancer, renal cell carcinoma, bladder cancer and Hodgkin's lymphoma.

Background References

1. Sato Y et al. The PD-1/PD-L1 axis may be aberrantly activated in occupational cholangiocarcinoma. Pathol Int N/A:N/A (2017).

2. Zhou ZH et al. The prognostic value and pathobiological significance of Glasgow microenvironment score in gastric cancer. J Cancer Res Clin Oncol N/A:N/A (2017).

Post-translational Modification

Ubiquitinated at Lys-233 by the SCF(FBXO38) complex, leading to its proteasomal degradation. Ubiquitinated via 'Lys-48'-linked polyubiquitin chains.; Tyrosine phosphorylated at Tyr-223 (within ITIM motif) and Tyr-248 (ITSM motif) upon ligand binding. Phosphorylation at Tyr-248 promotes the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta.; N-glycosylation at Asn-58 consists of two N-acetylglucosamine units and one fucose. N-glycosylation does not affect binding to nivolumab drug.

Subcellular Location

Membrane.

UNIPROT

SwissProt: Q15116 Human

Synonyms