PDCD1 gene

The PDCD1 gene (PDCD1 stands for Programmed Cell Death 1) is a protein-coding gene located on chromosome 2q37.3.

Programmed cell death-coded protein 1(PD-1) (PDCD1) is an immunoinhibitory receptor expressed in activated T cells. It is involved in the regulation of T cell functions, including those of CD8+ effector T cells. In addition, this protein can also promote the differentiation of CD4+ T cells into regulatory T cells.

The receptor protein PD-1 is expressed in many tumor types, including melanoma, and has been shown to play a role in anti-tumor immunity. In addition, this protein has been shown to be involved in protection against autoimmunity, but it may also contribute to the inhibition of effective anti-tumor and antimicrobial immunity.

The receptor protein PD1 is an inhibitory receptor on antigen-activated T cells that plays a crucial role in the induction and maintenance of immune tolerance to self (Fife BT et al. 2011).

The receptor protein PD1 provides inhibitory signals upon binding to the ligands CD274/PDCD1L1 and CD273/PDCD1LG2. Upon T cell receptor (TCR) binding, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T cell activation (By similarity). Suppresses T cell activation through recruitment of PTPN11/SHP-2: Upon ligand binding, PDCD1 is phosphorylated within the ITSM motif, leading to recruitment of the protein tyrosine phosphatase PTP N11/SHP-2, which mediates dephosphorylation of key proximal TCR signaling molecules such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta.

The interaction with CD274/PDCD1L1 (PD-L1 =PD-1 ligand) inhibits the effector function of cytotoxic T lymphocytes (CTLs) (Berger KN et al. 2018).

The PD-1-mediated inhibitory pathway is exploited by tumors to attenuate antitumor immunity and evade destruction by the immune system, thereby facilitating tumor survival. Tumor cells often camouflage themselves before elimination, e.g. by expressing the programmed death ligands PD-L1 and PD-L2 on their surface. An encounter of the PD-1 receptor protein with its ligand on activated T cells leads to a suppression of the antitumor immune response. The CD28 / CTLA-4 protein family thus acts as T-cell regulators and slows down T-cell activation after antigen stimulation. Compared to CTLA-4, the PD-1 receptor has a higher and broader selectivity for immunosuppressive signals that are triggered directly by tumor cells or the cells of the tumor stroma. It was therefore to be expected that modulation or antagonization of this regulatory mechanism (see PD-1 antibodies below) would have a higher antitumour efficiency than antagonization of the CTL-4 receptor protein (see ipilimumab below). Substances that pursue this approach are also referred to as "checkpoint modifiers" or "checkpoint inhibitors".

Blockade of the PDCD1-mediated pathway leads to reversal of the exhausted T cell phenotype and normalization of the antitumor response, providing a rationale for cancer immunotherapy

A humanized monoclonal antibody against the surface protein PD-1 is pembrolizumab, which is currently being used successfully in the KEYNOTE-002 trial in ipilimumab-resistant metastatic malignant melanoma.

Diseases associated with PD-1 include autoimmune disease with Mycobacterium tuberculosis and systemic lupus erythematosus.

The signaling pathways associated with PD-1 include the signaling pathways in various infectious diseases, including SARS-CoV-2 infection. Infectious diseases, including SARS-CoV-2 infection.