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Publication : Divergent effects of H-2K and H-2D genes on sensitivity of BL6 melanoma cells to NK cells or TNF-mediated cytotoxicity.

First Author  Kim M Year  1994
Journal  Cell Immunol Volume  155
Issue  2 Pages  358-71
PubMed ID  8181071 Mgi Jnum  J:18034
Mgi Id  MGI:66055 Doi  10.1006/cimm.1994.1129
Citation  Kim M, et al. (1994) Divergent effects of H-2K and H-2D genes on sensitivity of BL6 melanoma cells to NK cells or TNF-mediated cytotoxicity. Cell Immunol 155(2):358-71
abstractText  Transfection of BL6-8 (H-2Kb-,H-2Db+) and BL6-2 (H-2Kb-,H-2Db-) melanoma clones with H-2Kb or H-2Kd gene resulted in a stable augmentation of their sensitivity to lysis by NK cells or TNF-alpha that was associated with alterations of various phenotypic properties such as loss of endogenous A- and C-type retrovirus production and expression of melanoma-associated antigen and appearance of cell surface carbohydrates reacting with soybean agglutinin (SBA) and Grifonia simplicifolia 1-B4 (GS1B4) lectins. In contrast, transfection of the same clones with H-2Dd or H-2Ld gene did not reverse their resistance to NK cell- and TNF-mediated cytotoxicity and did not affect the phenotype of melanoma cells. These data suggest that the effect of H-2K gene on NK/TNF sensitivity of BL6 cells is indirect and it is closely associated with H-2K-induced phenotypic changes in these cells. To examine the possible role of the observed alterations of cell surface carbohydrates in augmentation of sensitivity of BL6 melanoma cells to lysis by NK cells or TNF, BL6-8 melanoma cells were transfected with cDNA encoding alpha 1,3-galactosyltransferase (alpha 1,3GT). Although the alpha 1,3GT gene-transfected cells expressed alpha-galactosyl epitopes reacting with GS1B4 lectin and reduced sialylation of cell membrane with unmasking SBA lectin-binding carbohydrates, they did not show an increase in tumor cell sensitivity to lysis by NK cells or TNF, indicating that H-2K gene-induced alterations in cell surface carbohydrate expression are not accountable for the observed increase in NK/TNF sensitivity of BL6 melanoma cells. It is possible that the H-2K gene-induced elimination of the endogenous retroviruses might be responsible for the observed increased sensitivity of BL6 melanoma cells to NK cell- and TNF-mediated cytotoxicity.
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