Format

Send to

Choose Destination
Immunol Rev. 2009 May;229(1):114-25. doi: 10.1111/j.1600-065X.2009.00767.x.

PD-1 signaling in primary T cells.

Author information

1
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, The University of Pennsylvania, Philadelphia, PA, USA. rileyj@exchange.upenn.edu

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.

PMID:
19426218
PMCID:
PMC3424066
DOI:
10.1111/j.1600-065X.2009.00767.x
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center