title: Recognition of the nonclassical MHC class I molecule H2-M3 by the receptor Ly49A regulates the licensing and activation of NK cells.
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.
authors.affiliation: Cancer Immunology Program, Trescowthick Laboratories, Peter MacCallum Cancer Centre, St. Andrews Place, East Melbourne, Australia. daniel.andrews@petermac.org
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Andrews
authors.forename: Lucy C
authors.initials: LC
authors.lastname: Sullivan
authors.forename: Nikola
authors.initials: N
authors.lastname: Baschuk
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Chan
authors.forename: Richard
authors.initials: R
authors.lastname: Berry
authors.forename: Claire L
authors.initials: CL
authors.lastname: Cotterell
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: Heloise
authors.initials: H
authors.lastname: Halse
authors.forename: Sally V
authors.initials: SV
authors.lastname: Watt
authors.forename: Jennifer
authors.initials: J
authors.lastname: Poursine-Laurent
authors.forename: Chyung-Ru
authors.initials: CR
authors.lastname: Wang
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Scalzo
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Yokoyama
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
mesh_terms: D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000378:metabolism*
chemical_list: C078177:H2-M3 antigen; D015395:Histocompatibility Antigens Class I; C527088:Klra1 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A