IFN-treated neuroblastoma cell lines remain resistant to T cell-mediated allo-killing, and susceptible to non-MHC-restricted cytotoxicity.
Neuroblastoma cell lines can have very low MHC Ag expression. The cell lines are insensitive to allo-killing by primed CTL, but are sensitive to non-MHC-restricted cytotoxicity. IFN-gamma increased class I expression, but the cells remained insensitive to CTL. Susceptibility to nonrestricted effectors was preserved. Class I+ glioma cell lines behaved similarly. The CTL resistance was localized to the recognition phase. Neuroblastoma lines did not form conjugates with primed T cells, but were lysed if they were coupled to the effectors via lectins. The levels of class I expression, and resistance to CTL, were constant over a range of IFN doses. HLA-A,B,C structure and distribution were studied more intensively on one cell line, CHP-100. HLA-A2 and -A3 were present on greater than or equal to 99% of the cells, in a unimodal distribution. After IFN treatment, the levels were similar to B cell controls. In two-dimensional gel electrophoresis, the molecules co-migrated with those of B cell controls. The defect may thus be in accessory proteins that are necessary for T cell recognition or binding, rather than in the structure or distribution of the HLA-A,B,C proteins.
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Children's Cancer Research Center, Children's Hospital, Philadelphia, PA.
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Lampson
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D002448:Cell Adhesion; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis / Q000235:genetics; D015234:HLA-A Antigens / Q000032:analysis; D015235:HLA-B Antigens / Q000032:analysis; D015236:HLA-C Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma; D008297:Male; D009447:Neuroblastoma / Q000276:immunology*; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000502:physiology
D000939:Epitopes; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D007371:Interferon-gamma