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 journalArticlepeer-review

140 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 languageEnglish
Pages (from-to)5693-5702
Number of pages10
JournalJournal of Immunology
Volume187
Issue number11
DOIs
StatePublished - 1 Dec 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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