Mouse CD94 participates in Qa-1-mediated self recognition by NK cells and delivers inhibitory signals independent of Ly-49.
Inhibitory receptors expressed on NK cells recognize MHC class I molecules and transduce negative signals to prevent the lysis of healthy autologous cells. The lectin-like CD94/NKG2 heterodimer has been studied extensively as a human inhibitory receptor. In contrast, in mice, another lectin-like receptor, Ly-49, was the only known inhibitory receptor until the recent discovery of CD94/NKG2 homologues in mice. Here we describe the expression and function of mouse CD94 analyzed by a newly established mAb. CD94 was detected on essentially all NK and NK T cells as well as small fractions of T cells in all mouse strains tested. Two distinct populations were identified among NK and NK T cells, CD94(bright) and CD94(dull) cells, independent of Ly-49 expression. The anti-CD94 mAb completely abrogated the inhibition of target killing mediated by NK recognition of Qa-1/Qdm peptide on target cells. Importantly, CD94(bright) but not CD94(dull) cells were found to be functional in the Qa-1/Qdm-mediated inhibition. In the presence of the mAb, activated NK cells showed substantial cytotoxicity against autologous target cells as well as enhanced cytotoxicity against allogeneic and "missing self" target cells. These results suggest that mouse CD94 participates in the protection of self cells from NK cytotoxicity through the Qa-1 recognition, independent of inhibitory receptors for classical MHC class I such as Ly-49.
Toyama-Sorimachi
N
N
Department of Immune Regulation, Tokyo Medical and Dental University, Graduate School, Tokyo, Japan. n-sori.mbch@med.tmd.ac.jp
Taguchi
Y
Y
Yagita
H
H
Kitamura
F
F
Kawasaki
A
A
Koyasu
S
S
Karasuyama
H
H
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000276:immunology; D019138:Antibodies, Blocking / Q000096:biosynthesis / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000494:pharmacology; D000918:Antibody Specificity; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000950:Antigens, Ly; D001666:Binding Sites, Antibody; D001667:Binding, Competitive / Q000276:immunology; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005314:Embryonic and Fetal Development / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010455:Peptides / Q000502:physiology; D055630:Receptors, NK Cell Lectin-Like; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000950:Antigens, Ly; D015395:Histocompatibility Antigens Class I; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010455:Peptides; C032907:Q surface antigens; C090580:Qdm protein, mouse; D055630:Receptors, NK Cell Lectin-Like; D001613:beta 2-Microglobulin