PD-1 signaling in primary T cells.

TLDR: This review focuses on exploring the hypothesis that PD‐1 ligation induces distinct signals during various stages of immune‐cell differentiation, and describing models to dissect the function of thePD‐1 cytoplasmic tail using primary cells in the absence of agonist antibodies.

Abstract: 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