Proliferating Cell Nuclear Antigen is a Novel Inhibitory Ligand for the Natural Cytotoxicity Receptor NKp44

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2011 Oct 25

PMID 22021614

Citations 128

Authors

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

Affiliations

Soon will be listed here.

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.

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