Relationship between antibody-dependent cell-mediated cytotoxicity due to anti-HTLV-1 and negative signal of major histocompatibility complex class I antigens on adult T-cell leukemia cell lines.
Natural killer (NK) cells possess two types of cytotoxic activity: natural killer cytotoxicity (NKC) and antibody-dependent cell-mediated cytotoxicity (ADCC). The NKC is regulated by the negative signal of the NK receptor, which recognizes major histocompatibility complex (MHC) class I antigens. However, it is not known whether or not the negative signal influences the ADCC. In this study, the relationship of the ADCC and negative signal was investigated. As target cells, adult T-cell leukemia (ATL) cell lines were used. When the target cells were treated with an anti-human T-lymphotropic virus type-1 (anti-HTLV-1) antibody, they were killed by the NK cells by means of the ADCC (ADCC/anti-HTLV-1). The killing levels were parallel with the cell surface HTLV-1 antigenicity. However, when these cells lines were treated with an anti-HLA, the ADCC (ADCC/anti-HLA) showed inverse correlation with the HLA antigenicity. Furthermore, when HLA polymorphic and monomorphic determinants of these target cells were blocked by F(ab')2 fragments of the anti-HLA and W6/32, the ADCC/anti-HLA was enhanced, but the ADCC/anti-HTLV-1 was not enhanced. These results suggest that the ADCC/anti-HLA may have an intimate relationship with the MHC class I antigens. The ADCC/anti-HLA may be suppressed by the negative signal. On the other hand, the ADCC/anti-HTLV-1 may have no relationship with the class I antigens and the negative signal may have no influence against the ADCC/anti-HTLV-1. The biological mechanism of this difference remains to be investigated.
Blood Transfusion Service, School of Medicine, Tokyo Medical and Dental University, Japan.
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Komatsu
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Tamiya
D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D006680:HLA Antigens / Q000187:drug effects / Q000276:immunology; D015481:HTLV-I Antibodies / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D015458:Leukemia, T-Cell / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000939:Epitopes; D006680:HLA Antigens; D015481:HTLV-I Antibodies; D015395:Histocompatibility Antigens Class I; D017452:Receptors, IgG; D007371:Interferon-gamma