Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44

Benyamin Rosental; Michael Brusilovsky; Uzi Hadad; Dafna Oz; Michael Y. Appel; Fabian Afergan; Rami Yossef; Lior Ann Rosenberg; Amir Aharoni; Adelheid Cerwenka; Kerry S. Campbell; Alex Braiman; Angel Porgador

doi:10.4049/jimmunol.1102267

Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44

Benyamin Rosental, Michael Brusilovsky, Uzi Hadad, Dafna Oz, Michael Y. Appel, Fabian Afergan, Rami Yossef, Lior Ann Rosenberg, Amir Aharoni, Adelheid Cerwenka, Kerry S. Campbell, Alex Braiman, Angel Porgador

Research output: Contribution to journal › Article › peer-review

166 Scopus citations

Abstract

NK cells play an important role in the early immune response to cancer. The NKp44 activating receptor is the only natural cytotoxicity receptor that is expressed exclusively by primate NK cells, yet its cellular ligands remain largely unknown. Proliferating cell nuclear Ag (PCNA) is overexpressed in cancer cells. In this study, we show that the NKp44 receptor recognizes PCNA. Their interaction inhibits NK cell function through NKp44/ITIM. The physical interaction of NKp44 and PCNA is enabled by recruitment of target cell PCNA to the NK immunological synapse. We demonstrate that PCNA promotes cancer survival by immune evasion through inhibition of NKp44-mediated NK cell attack.

Original language	English
Pages (from-to)	5693-5702
Number of pages	10
Journal	Journal of Immunology
Volume	187
Issue number	11
DOIs	https://doi.org/10.4049/jimmunol.1102267
State	Published - 1 Dec 2011

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.4049/jimmunol.1102267

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Rosental, B., Brusilovsky, M., Hadad, U., Oz, D., Appel, M. Y., Afergan, F., Yossef, R., Rosenberg, L. A., Aharoni, A., Cerwenka, A., Campbell, K. S., Braiman, A., & Porgador, A. (2011). Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44. Journal of Immunology, 187(11), 5693-5702. https://doi.org/10.4049/jimmunol.1102267

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title = "Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44",

abstract = "NK cells play an important role in the early immune response to cancer. The NKp44 activating receptor is the only natural cytotoxicity receptor that is expressed exclusively by primate NK cells, yet its cellular ligands remain largely unknown. Proliferating cell nuclear Ag (PCNA) is overexpressed in cancer cells. In this study, we show that the NKp44 receptor recognizes PCNA. Their interaction inhibits NK cell function through NKp44/ITIM. The physical interaction of NKp44 and PCNA is enabled by recruitment of target cell PCNA to the NK immunological synapse. We demonstrate that PCNA promotes cancer survival by immune evasion through inhibition of NKp44-mediated NK cell attack.",

author = "Benyamin Rosental and Michael Brusilovsky and Uzi Hadad and Dafna Oz and Appel, {Michael Y.} and Fabian Afergan and Rami Yossef and Rosenberg, {Lior Ann} and Amir Aharoni and Adelheid Cerwenka and Campbell, {Kerry S.} and Alex Braiman and Angel Porgador",

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doi = "10.4049/jimmunol.1102267",

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Rosental, B, Brusilovsky, M, Hadad, U, Oz, D, Appel, MY, Afergan, F, Yossef, R, Rosenberg, LA, Aharoni, A, Cerwenka, A, Campbell, KS, Braiman, A & Porgador, A 2011, 'Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44', Journal of Immunology, vol. 187, no. 11, pp. 5693-5702. https://doi.org/10.4049/jimmunol.1102267

TY - JOUR

T1 - Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44

AU - Rosental, Benyamin

AU - Brusilovsky, Michael

AU - Hadad, Uzi

AU - Oz, Dafna

AU - Appel, Michael Y.

AU - Afergan, Fabian

AU - Yossef, Rami

AU - Rosenberg, Lior Ann

AU - Aharoni, Amir

AU - Cerwenka, Adelheid

AU - Campbell, Kerry S.

AU - Braiman, Alex

AU - Porgador, Angel

PY - 2011/12/1

Y1 - 2011/12/1

N2 - NK cells play an important role in the early immune response to cancer. The NKp44 activating receptor is the only natural cytotoxicity receptor that is expressed exclusively by primate NK cells, yet its cellular ligands remain largely unknown. Proliferating cell nuclear Ag (PCNA) is overexpressed in cancer cells. In this study, we show that the NKp44 receptor recognizes PCNA. Their interaction inhibits NK cell function through NKp44/ITIM. The physical interaction of NKp44 and PCNA is enabled by recruitment of target cell PCNA to the NK immunological synapse. We demonstrate that PCNA promotes cancer survival by immune evasion through inhibition of NKp44-mediated NK cell attack.

AB - NK cells play an important role in the early immune response to cancer. The NKp44 activating receptor is the only natural cytotoxicity receptor that is expressed exclusively by primate NK cells, yet its cellular ligands remain largely unknown. Proliferating cell nuclear Ag (PCNA) is overexpressed in cancer cells. In this study, we show that the NKp44 receptor recognizes PCNA. Their interaction inhibits NK cell function through NKp44/ITIM. The physical interaction of NKp44 and PCNA is enabled by recruitment of target cell PCNA to the NK immunological synapse. We demonstrate that PCNA promotes cancer survival by immune evasion through inhibition of NKp44-mediated NK cell attack.

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U2 - 10.4049/jimmunol.1102267

DO - 10.4049/jimmunol.1102267

M3 - Article

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AN - SCOPUS:82755186747

SN - 0022-1767

VL - 187

SP - 5693

EP - 5702

JO - Journal of Immunology

JF - Journal of Immunology

IS - 11

ER -

Proliferating cell nuclear antigen is a novel inhibitory ligand for the natural cytotoxicity receptor NKp44

Abstract

ASJC Scopus subject areas

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