Sequential changes in MHC antigen expression induced by the v-Ki-ras oncogene

A series of early-passage cell lines were transformed with the v-Ki-ras oncogene with the aim of examining the effect of an activated ras gene on the ability of these cells to express major histocompatibility complex (MHC) antigens. These cell lines were found to undergo multiple phenotypic changes upon transformation and subsequent proliferation. At early passage, the predominant effect of ras was an increased ability to express class II antigens when induced with interferon gamma (IFN gamma). For class I antigens, maximum levels of expression induced with IFN gamma were largely unaffected, however, decreased sensitivity to induction with this lymphokine was noted. With subsequent in vitro or in vivo passage, both class I and class II antigen inducibility was attenuated. The latter phenotypic change was found to be transferable by coculture, implicating a soluble IFN gamma antagonist. Conditioned media from ras-transformed cells treated to activate their latent transforming growth factor beta (TGF beta) content mediated similar changes in MHC antigen inducibility, suggesting that TGF beta may be involved in modulating MHC antigen expression in ras-transformed cells.