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J Immunol. 2011 Dec 1;187(11):5693-702. doi: 10.4049/jimmunol.1102267. Epub 2011 Oct 21.

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

Author information

  • 1Shraga Segal Department of Microbiology and Immunology, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.

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.

PMID:
22021614
[PubMed - indexed for MEDLINE]
PMCID:
PMC3269963
Free PMC Article
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