Modulation by recombinant DNA leukocyte (alpha) and fibroblast (beta) interferons of the expression and shedding of HLA- and tumor-associated antigens by human melanoma cells.

Abstract

With a panel of monoclonal antibodies, the effect of recombinant human leukocyte interferons (i.e., IFN-alpha A, IFN-alpha D), of a hybrid leukocyte IFN (i.e., IFN-alpha A/D (Bg1)), and of recombinant fibroblast (beta) IFN on the expression and shedding of four types of melanoma-associated antigens (MAA) and of HLA antigens by the cultured melanoma cell line Colo 38 was investigated. None of the IFN affected the expression of the high m.w. melanoma-associated antigen (HMW-MAA), but all of them increased its shedding. The expression and shedding of the 115,000 MAA and of the 100,000 MAA were increased by IFN; the magnitude of the effect as well as the kinetics were different for the various IFN preparations. The cytoplasmic MAA was the most sensitive to modulation by IFN, because all four types increased its surface expression, its total content, and its shedding. The three types of leukocyte IFN, as well as the fibroblast IFN, were all effective in increasing the expression of HLA-A,B,C antigens, the effect being more marked on the free heavy chain than on the HLA-A,B,C complex. However, only leukocyte IFN enhanced the shedding of the HLA-A,B,C molecular complex. The three types of leukocyte IFN and especially fibroblast IFN enhanced the expression of the gene products of the HLA-D region, the effect being more marked on DC-1 antigens than on HLA-DR antigens. No effect on the shedding of HLA-DR and DC-1 antigens was detected.