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International Immunology Advance Access published online on July 2, 2007
International Immunology, doi:10.1093/intimm/dxm057
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

PD-1 and PD-1 ligands: from discovery to clinical application

Taku Okazaki1,2 and Tasuku Honjo2

1 21st Century Center of Excellence Formation
2 Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto 606-8501, Japan

Correspondence to: Correspondence to: T. Honjo; E-mail: honjo{at}mfour.med.kyoto-u.ac.jp

Programmed cell death-1 (PD-1, Pdcd1), an immunoreceptor belonging to the CD28/CTLA-4 family negatively regulates antigen receptor signaling by recruiting protein tyrosine phosphatase, SHP-2 upon interacting with either of two ligands, PD-L1 or PD-L2. Because of the wide range of ligand distribution in the body, its biological significance pervades almost every aspect of immune responses including autoimmunity, tumor immunity, infectious immunity, transplantation immunity, allergy and immunological privilege. In this review, we would like to summarize the history of PD-1 research since its discovery and recent findings that suggest promising future for the clinical application of PD-1 agonists and antagonists to various human diseases.

Keywords: Costimulation, Autoimmunity, Tumor immunity, Viral infection, SNP

Received 9 February 2007, accepted 23 April 2007.


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