Differential Up-Regulation of H-2D Versus H-2K Class I Major Histocompatibility Expression by Interferon-γ: 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-γ (IFN-γ). D^k expression was increased by IFN-γ as expected, but K^k expression remained at constitutive levels, despite treatment with a range of doses and times of exposure to IFN-γ. Analysis of somatic cell hybrids obtained by fusion of AKR SL3 with an H-2K^b and D^b IFN-γ augmentable partner tumor argued against the involvement of locus-specific, trans-acting factors as the basis for the nonaugmentable nature of the K^k 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-γ augmentable K^k and D^k genes. The uniform ability of IFN-γ to cause substantial increases in the expression of K^k 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 K^k nonaugmentation. These results are discussed with regard to the further study of AKR SL3 to better understand IFN-γ regulation of class I MHC expression.