Expression of p58.2 or CD94/NKG2A inhibitory receptors in an NK-like cell line, YTINDY, leads to HLA Class I-mediated inhibition of cytotoxicity in the p58.2- but not the CD94/NKG2A-expressing transfectant.
Natural killer cytotoxicity is down-regulated by HLA Class I-specific inhibitory receptors classified as killer inhibitory receptors (KIRs) or C-type lectins. The regulation of their inhibitory signaling pathways is not completely understood. The YTINDY NK-like cell line was transfected to express p58.2 KIR (YT/C143 transfectant) or CD94/NKG2A C-type lectin (YT/CD94 transfectant); and YT/C143, but not YT/CD94, cytotoxicity was down-regulated by Class I. YT/C143 and YT/CD94 expressed equally low p56(lck) levels, suggesting that p56(lck) is not absolutely required for p58.2 signaling but may be required for CD94/NKG2A signaling. Lower SHP-1 levels and activity were observed in YT/CD94 compared to YT/C143. However, increasing SHP-1 to equivalent levels in YT/C143 did not restore inhibition in YT/CD94. Our results suggest that the combination of low p56(lck) and SHP-1 levels may be responsible for the absent inhibitory signal in YT/CD94. In addition, the possible expression of CD94/NKG2C activating receptor may override inhibitory signals transduced through CD94/NKG2A.
Lin Chua
Hui
H
Department of Microbiology/Immunology, Indiana University School of Medicine, Riley Hospital, RM 0615, 702 Barnhill Drive, Indianapolis, IN 46202-5200, USA.
Brahmi
Zacharie
Z
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD / Q000096:biosynthesis*; D002352:Carrier Proteins / Q000032:analysis; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000032:analysis; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000032:analysis; D011506:Proteins; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D011975:Receptors, Mitogen / Q000037:antagonists & inhibitors / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction / Q000276:immunology; D000071176:Signaling Lymphocytic Activation Molecule Family; D014162:Transfection; D014407:Tumor Cells, Cultured
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C084093:CD244 protein, human; D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; C515078:KIR2DL3 protein, human; C527054:KLRC1 protein, human; C527059:KLRC2 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011506:Proteins; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054344:Receptors, KIR2DL3; D011975:Receptors, Mitogen; D055607:Receptors, Natural Killer Cell; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases