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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.

SUBMITTER: Rosental B

PROVIDER: S-EPMC3269963 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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

Rosental Benyamin B Brusilovsky Michael M Hadad Uzi U Oz Dafna D Appel Michael Y MY Afergan Fabian F Yossef Rami R Rosenberg Lior Ann LA Aharoni Amir A Cerwenka Adelheid A Campbell Kerry S KS Braiman Alex A Porgador Angel A

Journal of immunology (Baltimore, Md. : 1950) 20111021 11

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 ...[more]

PMID: 22021614

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