Recognition of the nonclassical MHC class i molecule H2-M3 by the receptor Ly49A regulates the licensing and activation of NK cells

Daniel M. Andrews*, Lucy C. Sullivan, Nikola Baschuk, Christopher J. Chan, Richard Berry, Claire L. Cotterell, Jie Lin, Heloise Halse, Sally V. Watt, Jennifer Poursine-Laurent, Chyung Ru Wang, Anthony A. Scalzo, Wayne M. Yokoyama, Jamie Rossjohn, Andrew G. Brooks, Mark J. Smyth

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

The development and function of natural killer (NK) cells is regulated by the interaction of inhibitory receptors of the Ly49 family with distinct peptide-laden major histocompatibility complex (MHC) class I molecules, although whether the Ly49 family is able bind to other MHC class I-like molecules is unclear. Here we found that the prototypic inhibitory receptor Ly49A bound the highly conserved nonclassical MHC class I molecule H2-M3 with an affinity similar to its affinity for H-2D d. The specific recognition of H2-M3 by Ly49A regulated the 'licensing' of NK cells and mediated 'missing-self' recognition of H2-M3-deficient bone marrow. Host peptide-H2-M3 was required for optimal NK cell activity against experimental metastases and carcinogenesis. Thus, nonclassical MHC class I molecules can act as cognate ligands for Ly49 molecules. Our results provide insight into the various mechanisms that lead to NK cell tolerance.

Original languageEnglish (US)
Pages (from-to)1171-1177
Number of pages7
JournalNature Immunology
Volume13
Issue number12
DOIs
StatePublished - Dec 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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