Effect of cellular density and viral oncogenes on the major histocompatibility complex class I antigen response to gamma-interferon in BALB-c/3T3 cells

Abstract

Cellular density in culture has profound effects on major histocompatibility complex (MHC) class I antigen expression in BALB/c-3T3 cells. Cells which have been confluent for greater than 24 h demonstrate a 2- to 6-fold increase in MHC class I antigen expression compared to subconfluent cells. These density-associated changes in MHC class I antigen expression occur both in untransformed and in v-mos or v-rasKi-transformed cells. The density-associated increases are specific for MHC class I antigens and do not occur with the cytoskeletal antigen actin. Transformation of the BALB/c-3T3 cells by either v-rasKi or v-mos has little or no direct effect on MHC class I expression under standard culture conditions. However, both oncogenes can indirectly alter the enhancement of MHC class I antigen expression in response to gamma-interferon. Incubation of untransformed BALB/c-3T3 cells with gamma-interferon leads to greater relative and absolute increases in MHC class I antigen expression in confluent cells than it does in subconfluent cells. In contrast, in v-rasKi- and v-mos-transformed cells, the subconfluent cells have a greater increase in MHC class I antigen expression in response to gamma-interferon than the cells which have exceeded monolayer confluence. The dense v-rasKi- and v-mos-transformed BALB/c-3T3 cell cultures are able to deplete their medium of the exogenous gamma-interferon, and this depletion of gamma-interferon causes the increase in the MHC class I antigen expression to be less sustained with lower peak expressions than the expression found in subconfluent cells. Supplementation with additional gamma-interferon can restore the full enhancement of MHC class I antigen in the transformed BALB/c-3T3 cells. The v-mos- and v-rasKi-transformed cells are more likely to deplete their medium of exogenous gamma-interferon because these cells can exceed monolayer confluence and thus achieve 10-fold higher densities than the untransformed BALB/c-3T3 cells. At high cellular densities, untransformed cells can partially deplete their medium of exogenous gamma-interferon, but this phenomenon is generally less pronounced than in the transformed cells.