PDCD1
GeneName
PDCD1
Summary
PDCD1, also known as PD-1 or programmed cell death protein 1, is a 32 kDa transmembrane protein predominantly expressed on the surface of activated T cells, B cells, and regulatory T cells. It is located on the external side of the plasma membrane and functions as an immune checkpoint receptor that negatively regulates immune responses. PDCD1 plays a crucial role in the adaptive immune response by inhibiting T cell activation and promoting apoptotic processes in immune cells, thereby maintaining immune homeostasis and preventing autoimmunity.
Importance
PDCD1 is relevant to: - Immune checkpoint therapy, particularly in cancer treatment, as it is a target for monoclonal antibodies that enhance T cell responses against tumours - Autoimmune diseases, where its regulatory function is implicated in the tolerance of self-antigens - Infectious diseases, as PD-1 expression is associated with T cell exhaustion during chronic infections - The development of vaccines, as modulation of PD-1 can improve vaccine efficacy by enhancing T cell responses
Top Products
For researchers investigating PDCD1, we recommend two primary antibodies that stand out for their performance and reliability. The first is the well-cited Anti-PD1 antibody [NAT105] (ab52587), a monoclonal antibody that has garnered 315 citations, reflecting its strong reputation in the field. This antibody is versatile, suitable for flow cytometry (FC), immunohistochemistry (IHC), western blotting (WB), and immunocytochemistry (ICC), making it an excellent choice for various experimental needs.Additionally, we offer the recombinant antibody, Anti-PD1 antibody [EPR4877(2)] (ab137132), which has been validated for use in immunohistochemistry (IHC) and has 127 citations. The recombinant nature of this antibody ensures batch-to-batch consistency, providing researchers with a reliable option for PDCD1 detection. Together, these antibodies provide robust tools for studying PDCD1 in diverse applications. The Recombinant Human PD1 protein ELISA Kit (ab280753) is an excellent option for researchers looking to measure PDCD1 levels in their samples.
Abcam Product Citation Summary
The data indicates that the PDCD1 antibody (ab52587) has been utilised in various studies focusing on human LLABCs and bovine models. The antibody was primarily applied in immunohistochemistry (IHC) for human samples and in western blotting (WB) for bovine samples, particularly in the context of BVDV infections.
Abcam Product Citation Table
Developmental stage
Induced at programmed cell death.
Function
Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:31754127, PubMed:32184441, PubMed:37208329). Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:21276005, PubMed:26602187). Following T-cell receptor (TCR) engagement, PDCD1 associates with TCR-CD3 in the immunological synapse and directly inhibits T-cell activation (PubMed:32184441). 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 (PubMed:32184441).
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 (PubMed:28951311). The interaction with CD274/PDCD1L1 inhibits cytotoxic T lymphocytes (CTLs) effector function (PubMed:28951311). 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 (PubMed:22658127, PubMed:25034862, PubMed:25399552).
Involvement in disease
Autoimmune disease, multisystem, infantile-onset, 4
ADMIO4
An autosomal recessive immunologic disorder characterized by lymphoproliferative autoimmunity and onset of various autoimmune diseases in early childhood. Death from autoimmune pneumonitis may occur.
None
The disease may be caused by variants affecting the gene represented in this entry. PDCD1 deficiency due to a homozygous frameshift mutation has been detected in a patient with severe tuberculosis and autoimmunity. The patient had depletion and dysfunction of multiple T and NK lymphocyte subsets and impaired gamma-IFN production.
Post-translational modifications
Ubiquitinated at Lys-233 by the SCF(FBXO38) complex, leading to its proteasomal degradation (PubMed:30487606). Ubiquitinated via 'Lys-48'-linked polyubiquitin chains (PubMed:30487606). Deubiquitinated and thus stabilized by USP5 (PubMed:37208329).
Tyrosine phosphorylated at Tyr-223 (within ITIM motif) and Tyr-248 (ITSM motif) upon ligand binding (PubMed:31754127, PubMed:32184441). Phosphorylation at Tyr-248 by FYN 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 (PubMed:32184441). Phosphorylation at Thr-234 promotes the recruitment of the deubiquitinase USP5 (PubMed:37208329).
N-glycosylation at Asn-58 contains at least two N-acetylglucosamine units and one fucose (PubMed:28165004). N-glycosylation does not affect binding to nivolumab drug (PubMed:28165004).
Cellular localization
- Cell membrane
- Single-pass type I membrane protein
Alternative names
CD279, PD1, PDCD1, Programmed cell death protein 1, Protein PD-1, hPD-1
Database links
Other research areas
- Immunology & Infectious Disease