2009/04/21 by James L. Riley · 2 citations
Immunology and Microbiology · Medicine · #Immune Cell Function and Interaction #T-cell and B-cell Immunology #Cancer Immunotherapy and Biomarkers #Signal transduction #Biology #Cell biology #Cytotoxic T cell #T cell #Immune system #Ligation #Cell signaling #Phosphorylation #T-cell receptor #Cytokine #Immunology #Molecular biology #Biochemistry
paper · doi:10.1111/j.1600-065x.2009.00767.x
openalex publication_date 2009/04/21 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/06
SUMMARY: Programmed death-1 (PD-1) is a cell surface molecule that regulates the adaptive immune response. Engagement of PD-1 by its ligands PD-L1 or PD-L2 transduces a signal that inhibits T-cell proliferation, cytokine production, and cytolytic function. While a great deal is known concerning the biologic roles PD-1 plays in regulating the primary immune response and in T-cell exhaustion, comparatively little is known regarding how PD-1 ligation alters signaling pathways. PD-1 ligation is known to inhibit membrane-proximal T-cell signaling events, while ligation of the related inhibitory molecule cytotoxic T-lymphocyte antigen-4 appears to target more downstream signaling pathways. A major obstacle to an in-depth understanding of PD-1 signaling is the lack of physiologic models in which to study signal transduction. This review focuses on: (i) signaling pathways altered by PD-1 ligation, (ii) factors recruited upon PD-1 phosphorylation, and (iii) exploring the hypothesis that PD-1 ligation induces distinct signals during various stages of immune-cell differentiation. Lastly, we describe models to dissect the function of the PD-1 cytoplasmic tail using primary cells in the absence of agonist antibodies.