Differential H-2 antigen expression in teratocarcinoma-fibroblast hybrids

Embryo-derived teratocarcinoma cells, like early embryonic cells, do not express the classical MHC class I antigens. The mRNAs for both the H-2 α chain and β₂-microglobulin are also undetectable in these cells. We observed that upon fusion of H-2-negative mouse P19 teratocarcinoma cells (H-2(k) allotype) with H-2-positive embryonic fibroblasts of C57BL/6 origin (H-2^b allotype), teratocarcinoma-like cell hybrids were obtained which express the H-2K^b antigen derived from the embryonic fibroblasts, but not the H-2K(k)D(k) antigens of the teratocarcinoma. This finding demonstrates that the teratocarcinoma H-2 genes do not respond to the positive regulatory factors present in the hybrids. The H-2(k) allele was not lost during fusion, as shown by its expression in retinoic-acid-differentiated hybrids treated with interferon-γ (10 U/ml, 4 days). H-2K(k)D(k) antigen expression could also be induced in the undifferentiated hybrids by treating the cells with the protein synthesis inhibitor cycloheximide (1-10 μg/ml, 18 h), but not with the demethylating agent 5-azacytidine (5 μM, 2-4 days). These data suggest the presence of a labile, negative regulating protein factor which selectively prevents the expression of the teratocarcinoma-derived H-2 antigens. When the level of this factor(s) is reduced, the teratocarcinoma H-2 genes are capable of responding to the positive regulatory factors.