Molecular analysis of deficient class I H-2 antigen expression by mouse lung carcinoma cells.
We have continued our investigations of line lung carcinoma cells to understand the molecular basis of decreased expression of class I H-2 Ag and class I Ag induction with DMSO. We show that line 1, a murine lung carcinoma cell line, has low levels of class I Ag (H-2K, D, and L) because it is deficient in both class I and beta 2-microglobulin (B2M) RNA, and that these mRNA can be coordinately induced with DMSO. Evidence presented herein also shows that IFN-gamma can induce surface expression of class I Ag and suggests that it may act through a different mechanism than DMSO in inducing class I Ag. To further evaluate the regulation of class I expression, H-2Dp genes were transfected into line 1 cells. The transfected H-2 genes appear to be constitutively expressed at much higher levels than are the endogenous class I genes because surface expression of the foreign Dp Ag on the transfectants is elevated relative to the endogenous H-2d haplotype class I Ag. Both Dp surface expression and Dp mRNA are induced after treatment with DMSO. In all the Dp transfectants, we observed higher constitutive levels of class I mRNA as well as increased constitutive levels of endogenous B2M mRNA when compared to control or untransfected line 1 cells, however, we could not correlate these constitutive levels with Dp copy number. These results suggest that the regulation of class I and B2M genes is linked and that expression of class I genes can affect the expression of B2M genes.
D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005805:Genes, MHC Class I / Q000187:drug effects; D006183:H-2 Antigens / Q000096:biosynthesis* / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008175:Lung Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012313:RNA / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection / Q000187:drug effects; D001613:beta 2-Microglobulin / Q000235:genetics
D006183:H-2 Antigens; D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D012313:RNA; D007371:Interferon-gamma; D004121:Dimethyl Sulfoxide