PD-1 signaling in primary T cells

By James L. Riley. Immunological Reviews, 2009

764 citations recorded by the source corpus.

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.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/ca7789e1603c58cd27d2dea719ab18bda06d6d30

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Arlene H. Sharpe
2. I. Mellman
3. G. Freeman
4. George Coukos
5. Loise M. Francisco
6. W. Zou
7. P. Sage
8. T. Welling

In Oncology

1. Arlene H. Sharpe
2. G. Freeman
3. I. Mellman
4. W. Zou
5. Loise M. Francisco
6. P. Sage
7. T. Welling
8. Zhigang Tian

Citations in the corpus

• Dual Blockade of PD-1 and CTLA-4 Combined with Tumor Vaccine Effectively Restores T Cell Rejection Function in Tumors (2013, background): “Studies report that PD-1 mediates inhibition by blocking phosphoinositide 3-kinase (PI3K) activation, whereas CTLA-4 functions through binding to the phosphatase PP2A, leading to inhibition of Akt phosphorylation (29, 59, 63, 64).”
• T cell anergy, exhaustion, senescence and stemness in the tumor microenvironment (2013, background): “Although the detailed molecular mechanism of T cell exhaustion is incompletely defined, it is suggested that recruitment of SH2-domain containing protein tyrosine phosphatases (SHP-1 and/or SHP-2) to the immunoreceptor tyrosinebased switch motif (ITSM) within the PD-1 cytoplasmic tail inhibits signa”
• T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition (2016, background): “PD-1 has been shown to co-immunoprecipitate with tyrosine phosphatases Shp2, Shp1, and the Lck-inhibiting kinase Csk from cell lysates (20), and contains a structural motif that might recruit the lipid phosphatase SHIP-1 (27).”
• The PD-1 Pathway in Tolerance and Autoimmunity (2010, background): “Engagement of PD1 by either of its ligands during TCR signaling can block T-cell proliferation, cytokine production and cytolytic function, and impair T-cell survival (19).”
• Overview of the Immune Response (2003, background): “In addition, a specific receptor-ligand pair, programmed death 1 and programmed death ligand 1, transduces signals to the activated lymphocyte to inhibit its proliferation and effector functions, thus extinguishing the Tcell response.(52) Mutations affecting the function of many of the molecules inv”