title: Stochastic acquisition of Qa1 receptors during the development of fetal NK cells in vitro accounts in part but not in whole for the ability of these cells to distinguish between class I-sufficient and class I-deficient targets.
abstract: Fetal mouse NK cells are grossly deficient in the expression of Ly49 molecules yet show a limited ability to distinguish between wild-type and MHC class I-deficient target cells. In this paper we report that during their development in vitro from immature thymic progenitors, a proportion of C57BL/6 fetal NK cells acquires receptors for a soluble form of the nonclassical class I molecule Qa1b associated with the Qdm peptide, but not for soluble forms of the classical class I molecules Kb and Db. The acquisition of these Qa1 receptors occurs in a stochastic manner that is strictly controlled by cytokines, and in particular is strongly inhibited by IL-4. All fetal NK clones tested, including those that lack detectable Qa1 receptors, express mRNA for CD94 and for both inhibitory and noninhibitory members of the NKG2 family. Fetal NK cells lacking receptors for Qa1 (and also for classical class I molecules) cannot distinguish between wild-type and class I-deficient blasts but, surprisingly, distinguish efficiently between certain wild-type and class I-deficient tumor cells. A variant line that lacks several members of the NKG2 family kills both types of tumor cell equally well, suggesting the existence of NKG2-containing inhibitory receptors that recognize as yet undefined nonclassical class I molecules of restricted distribution.
authors.affiliation: Department of Microbiology and Immunology, The Medical School, Newcastle, United Kingdom.
authors.forename: J A
authors.initials: JA
authors.lastname: Toomey
authors.forename: M
authors.initials: M
authors.lastname: Salcedo
authors.forename: L A
authors.initials: LA
authors.lastname: Cotterill
authors.forename: M M
authors.initials: MM
authors.lastname: Millrain
authors.forename: Z
authors.initials: Z
authors.lastname: Chrzanowska-Lightowlers
authors.forename: J
authors.initials: J
authors.lastname: Lawry
authors.forename: K
authors.initials: K
authors.lastname: Fraser
authors.forename: F
authors.initials: F
authors.lastname: Gays
authors.forename: J H
authors.initials: JH
authors.lastname: Robinson
authors.forename: S
authors.initials: S
authors.lastname: Shrestha
authors.forename: P J
authors.initials: PJ
authors.lastname: Dyson
authors.forename: C G
authors.initials: CG
authors.lastname: Brooks
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D002448:Cell Adhesion / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D016207:Cytokines / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005314:Embryonic and Fetal Development / Q000276:immunology*; D006183:H-2 Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D051920:NK Cell Lectin-Like Receptor Subfamily D; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D055607:Receptors, Natural Killer Cell; D012995:Solubility; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013269:Stochastic Processes; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; C032907:Q surface antigens; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell