Differential up-regulation of H-2D versus H-2K class I major histocompatibility expression by interferon-gamma: evidence against a trans-acting allele-specific factor.
Previous investigation described a unique differential phenotype for the murine T-cell tumor AKR SL3 with regard to augmentation of class I major histocompatibility complex antigen expression by interferon-gamma (IFN-gamma). Dk expression was increased by IFN-gamma as expected, but Kk expression remained at constitutive levels, despite treatment with a range of doses and times of exposure to IFN-gamma. Analysis of somatic cell hybrids obtained by fusion of AKR SL3 with an H-2Kb and Db IFN-gamma augmentable partner tumor argued against the involvement of locus-specific, trans-acting factors as the basis for the nonaugmentable nature of the Kk gene in AKR SL3. Here, we provide evidence against the remaining possibility of an allele-specific, negative-acting factor in AKR SL3. Hybrids were constructed between drug-marked sublines of AKR SL3 and the R1.G1 T-cell tumor which carries IFN-gamma augmentable Kk and Dk genes. The uniform ability of IFN-gamma to cause substantial increases in the expression of Kk in hybrid populations and a large number of hybrid clones from three separate fusions indicated that a trans-acting, negative factor was not present in AKR SL3. Rather, these data coupled with Northern analysis were consistent with cis alterations operating at the level of transcription as the basis for Kk nonaugmentation. These results are discussed with regard to the further study of AKR SL3 to better understand IFN-gamma regulation of class I MHC expression.
Rich
R F
RF
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03756.
Gaffney
K J
KJ
White
H D
HD
Green
W R
WR
D000483:Alleles; D000818:Animals; D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D002459:Cell Fusion; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006183:H-2 Antigens / Q000096:biosynthesis* / Q000235:genetics; D006822:Hybrid Cells; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins; D012097:Repressor Proteins / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D007371:Interferon-gamma