Cutting edge: expression of functional CD94/NKG2A inhibitory receptors on fetal NK1.1+Ly-49- cells: a possible mechanism of tolerance during NK cell development.
Fetal liver- and thymus-derived NK1.1+ cells do not express known Ly-49 receptors. Despite the absence of Ly-49 inhibitory receptors, fetal and neonatal NK1.1+Ly-49- cells can distinguish between class Ihigh and class Ilow target cells, suggesting the existence of other class I-specific inhibitory receptors. We demonstrate that fetal NK1. 1+Ly-49- cell lysates contain CD94 protein and that a significant proportion of fetal NK cells are bound by Qa1b tetramers. Fetal and adult NK cells efficiently lyse lymphoblasts from Kb-/-Db-/- mice. Qa1b-specific peptides Qdm and HLA-CW4 leader peptide specifically inhibited the lysis of these blasts by adult and fetal NK cells. Qdm peptide also inhibited the lysis of Qa1b-transfected human 721.221 cells by fetal NK cells. Taken together, these results suggest that the CD94/NKG2A receptor complex is the major known inhibitory receptor for class I (Qa1b) molecules on developing fetal NK cells.
Sivakumar
P V
PV
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235, USA. sivakuma@utsw.swmed.edu
Gunturi
A
A
Salcedo
M
M
Schatzle
J D
JD
Lai
W C
WC
Kurepa
Z
Z
Pitcher
L
L
Seaman
M S
MS
Lemonnier
F A
FA
Bennett
M
M
Forman
J
J
Kumar
V
V
D000375:Aging / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000096:biosynthesis*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000950:Antigens, Ly; D000954:Antigens, Surface; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002474:Cell-Free System / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000235:genetics; D005333:Fetus; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D007106:Immune Sera / Q000737:chemistry; D007108:Immune Tolerance / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type; D008099:Liver / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D055651:NK Cell Lectin-Like Receptor Subfamily B; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D011485:Protein Binding / Q000276:immunology; D014176:Protein Biosynthesis; D011506:Proteins; D055630:Receptors, NK Cell Lectin-Like; D013154:Spleen / Q000166:cytology / Q000254:growth & development / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured
D000941:Antigens; D015703:Antigens, CD; D000950:Antigens, Ly; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I; D007106:Immune Sera; C527203:KLRB1 protein, human; C527211:Klrb1c protein, mouse; C497870:Klrd1 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010455:Peptides; D011506:Proteins; C032907:Q surface antigens; D055630:Receptors, NK Cell Lectin-Like