Transfection of beta 2-microglobulin restores IFN-mediated protection from natural killer cell lysis in YAC-1 lymphoma variants.
A beta 2-microglobulin (beta 2m)-deficient variant of YAC-1, A.H-2-, was transfected with a genomic beta 2m clone. Transfected cells were used to investigate the role of beta 2m in IFN-induced protection from NK cell lysis. IFN-gamma treatment of the NK-sensitive murine YAC-1 lymphoma results in reduced sensitivity to NK cell-mediated lysis in parallel with increased expression of its constitutively low MHC class I expression. It was previously shown that the A.H-2- variant had lost both these capacities, although it retained other responses to IFN-gamma. Here beta 2m transfection restored the YAC-1 phenotype with respect to an inducible expression of MHC class I molecules and a concomitant protection from NK cell lysis after treatment with IFN-gamma. In the absence of IFN-gamma the NK sensitivity of the transfectants did not differ significantly from A.H-2-. A similar protection from NK cell lysis, in parallel with enhanced MHC class I expression, was observed for in vivo-passaged beta 2m transfectants whereas no protection was found for in vivo-passaged A.H-2- cells. The present study provides evidence that the IFN-gamma-mediated protection from NK cell lysis is dependent on beta 2m expression in the YAC-1 lymphoma. Restoration of MHC class I assembly, transport, and concomitantly an IFN-gamma augmentable cell surface expression of MHC class I molecules is a possible explanation for the effect of beta 2m.
Ljunggren
H G
HG
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Sturmhöfel
K
K
Wolpert
E
E
Hämmerling
G J
GJ
Kärre
K
K
D000818:Animals; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000502:physiology*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008223:Lymphoma / Q000276:immunology*; D051379:Mice; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000235:genetics / Q000502:physiology*
D006183:H-2 Antigens; D001613:beta 2-Microglobulin; D007371:Interferon-gamma