Role of Qa-1(b)-binding receptors in the specificity of developing NK cells.
NK cells acquire the ability to recognize MHC class I molecules during development. Studies with Qa-1(b) tetramers (Qa-1 tetramers) showed that nearly all NK1.1(+) cells from newborn C57BL/6 mice express Qa-1-binding receptors. Cytotoxic activity of these cells is fully inhibited by Qa-1 ligands on target cells. In contrast, neither receptors for H-2K(b) nor H-2D(b) were observed on NK1.1(+) cells from newborn mice. After birth, frequencies of Qa-1 tetramer(+)/ NK1.1(+) cells gradually decrease as the number of Ly49(+) /NK1.1(+) cells increases. Cell transfer studies showed that Qa-1 tetramer(+) cells from newborn mice do not lose expression of Qa-1 receptors, but that they further acquire expression of Ly49 molecules. Acquisition of Qa-1-binding receptors appears largely independent of host MHC class I molecules, as observed in studies using beta2-microglobulin-deficient (beta2m(-/-)) mice as well as K(b)/ D(b-/-) and K(b)/D(b)/beta2m(-/-) mice. The present results suggest that Qa-1-binding receptors play an important role in the specificity of developing NK cells, and suggest that these cells rely mainly on inhibitory receptors specific for non-classical MHC class I molecules to maintain self tolerance during the first weeks of life.
Salcedo
M
M
Unité de Biologie Moléculaire du Gène, INSERM U277, Institut Pasteur, Paris, France. msalcedo@idm-biotech.com
Colucci
F
F
Dyson
P J
PJ
Cotterill
L A
LA
Lemonnier
F A
FA
Kourilsky
P
P
Di Santo
J P
JP
Ljunggren
H G
HG
Abastado
J P
JP
D019264:Adoptive Transfer; D000375:Aging / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D000950:Antigens, Ly; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D004268:DNA-Binding Proteins; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D007739:L Cells; D037181:Lectins, C-Type; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism*; D055630:Receptors, NK Cell Lectin-Like; D017634:Self Tolerance / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000235:genetics
C105661:8-phenyl-2-(di-n-propylamino)tetralin; D000950:Antigens, Ly; D004268:DNA-Binding Proteins; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D037181:Lectins, C-Type; D008024:Ligands; D010455:Peptides; C032907:Q surface antigens; C499308:Rag2 protein, mouse; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D013764:Tetrahydronaphthalenes; C064655:V(D)J recombination activating protein 2; D001613:beta 2-Microglobulin