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Proc Natl Acad Sci U S A. 2018 Nov 6;115(45):11579-11584. doi: 10.1073/pnas.1722374115. Epub 2018 Sep 24.

Critical role for the Ly49 family of class I MHC receptors in adaptive natural killer cell responses.

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Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Laboratory Science, Taibah University, Medina 42353, Kingdom of Saudi Arabia.
Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON K1N 6N5, Canada;


Adaptive natural killer (NK) cell memory represents a new frontier in immunology. Work over the last decade has discovered and confirmed the existence of NK cells with antigen-specific memories, which had previously been considered a unique property of T and B cells. These findings have shown that antigen-specific NK cells gain their specificity without the use of RAG proteins, representing a novel mechanism for generating antigen specificity, but the details of this mechanism have remained a mystery. We have discovered that members of the Ly49 family of surface receptors are critically involved in both the sensitization and the challenge phases of an NK cell memory response, as is antigen presentation from their binding partner, the class I MHC. Moreover, we demonstrate that the Ly49-interacting component of a presented antigen dictates the specificity of the NK cell memory response, implicating Ly49 receptors themselves in antigen-specific recognition. Finally, we demonstrate that adaptive NK cell memories can protect against an otherwise lethal melanoma without T cell or B cell support. These findings offer insight into the mechanism behind NK cell antigen specificity and demonstrate the clinical potential of this adaptive immune cell.


Ly49 receptors; adaptive memory; cancer vaccines; immune memory; natural killer cells

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no conflict of interest.

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