Journal ArticleDOI
PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70/CD3ζ signalosome and downstream signaling to PKCθ
Kelly-Ann Sheppard,Lori Fitz,Julie M. Lee,Christina Benander,Judith A. George,Joe Wooters,Yongchang Qiu,Jason Jussif,Laura L. Carter,Clive Wood,Divya Chaudhary +10 more
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TLDR
It is demonstrated that PD‐1 modulation of T‐cell function involves inhibition of TCR‐mediated phosphorylation of ZAP70 and association with CD3ζ andPD‐1 signaling attenuates PKCθ activation loop phosphorylated in a cognate TCR signal.About:
This article is published in FEBS Letters.The article was published on 2004-09-10. It has received 627 citations till now. The article focuses on the topics: Immunoreceptor tyrosine-based activation motif & Immunoreceptor tyrosine-based inhibitory motif.read more
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Journal ArticleDOI
PD-1 and its ligands in tolerance and immunity
TL;DR: Current understanding of the immunoregulatory functions of PD-1 and its ligands and their therapeutic potential are discussed and an inhibitory bidirectional interaction between PD-L1 and B7-1 is discovered, revealing new ways the B7:CD28 family regulates T cell activation and tolerance.
Journal ArticleDOI
Molecular mechanisms of T cell co-stimulation and co-inhibition
TL;DR: The mechanisms through which T cell activation, differentiation and function is controlled by co-stimulatory and co-inhibitory receptors are reviewed.
Journal ArticleDOI
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy
TL;DR: The current state of understanding of T-cell costimulatory mechanisms and checkpoint blockade, primarily of CTLA4 and PD-1, is reviewed, and conceptual gaps in knowledge are highlighted.
Journal ArticleDOI
The PD-1 pathway in tolerance and autoimmunity
TL;DR: This review highlights how PD‐1 and its ligands defend against potentially pathogenic self‐reactive effector T cells by simultaneously harnessing two mechanisms of peripheral tolerance: (i) the promotion of Treg development and function and (ii) the direct inhibition of potentially pathogen self-reactive T cells that have escaped into the periphery.
Journal ArticleDOI
CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms
Richard V. Parry,Jens M. Chemnitz,Kenneth A. Frauwirth,Anthony R. Lanfranco,Inbal Braunstein,Sumire V. Kobayashi,Peter S. Linsley,Craig B. Thompson,James L. Riley +8 more
TL;DR: In this paper, CTLA-4 and PD-1 signaling inhibited Akt phosphorylation by preventing CD3/CD28-mediated upregulation of glucose metabolism and Akt activity, but each accomplished this regulation using separate mechanisms.
References
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Journal ArticleDOI
Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.
Gordon J. Freeman,Andrew J. Long,Yoshiko Iwai,Karen Bourque,Tatyana Chernova,Hiroyuki Nishimura,Lori Fitz,Nelly Malenkovich,Taku Okazaki,Michael C. Byrne,Heidi F. Horton,Lynette A. Fouser,Laura L. Carter,Vincent Ling,Michael R Bowman,Beatriz M. Carreno,Mary Collins,Clive Wood,Tasuku Honjo +18 more
TL;DR: It is reported here that the ligand of PD-1 (PD-L1), an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells, is a member of the B7 gene family.
Journal ArticleDOI
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Yvette Latchman,Clive Wood,Tatyana Chernova,Divya Chaudhary,Madhuri Borde,Irene Chernova,Yoshiko Iwai,Andrew J. Long,Julia A. Brown,Raquel A. Nunes,Edward A. Greenfield,Karen Bourque,Vassiliki A. Boussiotis,Laura L. Carter,Beatriz M. Carreno,Nelly Malenkovich,Hiroyuki Nishimura,Taku Okazaki,Tasuku Honjo,Arlene H. Sharpe,Gordon J. Freeman +20 more
TL;DR: These studies show overlapping functions of PD-L1 andPD-L2 and indicate a key role for the PD- L–PD-1 pathway in regulating T cell responses.
Journal ArticleDOI
Autoimmune Dilated Cardiomyopathy in PD-1 Receptor-Deficient Mice
Hiroyuki Nishimura,Taku Okazaki,Yoshimasa Tanaka,Kazuki Nakatani,Masatake Hara,Akira Matsumori,Shigetake Sasayama,Akira Mizoguchi,Hiroshi Hiai,Nagahiro Minato,Tasuku Honjo +10 more
TL;DR: Results indicate that PD-1 may be an important factor contributing to the prevention of autoimmune diseases and high-titer circulating IgG autoantibodies reactive to a 33-kilodalton protein expressed specifically on the surface of cardiomyocytes.
Journal ArticleDOI
Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes
Yasutoshi Agata,Akemi Kawasaki,Hiroyuki Nishimura,Yasumasa Ishida,Takeshi Tsubata,Hideo Yagita,Tasuku Honjo +6 more
TL;DR: The results suggest that the expression of thePD-1 antigen is tightly regulated and induced by signal transduction through the antigen receptor and do not exclude the possibility that the PD- 1 antigen may play a role in clonal selection of lymphocytes although PD-1 expression is not required for the common pathway of apoptosis.
Journal ArticleDOI
The ‘Shp'ing news: SH2 domain-containing tyrosine phosphatases in cell signaling
TL;DR: A small, highly conserved subfamily of protein-tyrosine phosphatases, members of which are present in both vertebrates and invertebrates, and the key targets of each Shp have remained elusive are identified.
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Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.
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