Induction by human interferon and murine h-2l(d) gene of the surface expression of endogenous hla class-I free heavy-chains in hct human colon-carcinoma cells, deficient in Beta-2-microglobulin.

The colon cancer cell line HCT fails to express HLA class I antigens on the cell surface as a consequence of two independent mutations occurring in both copies of the beta2-microglobulin (beta2-mu) gene. Restoration of HLA class I antigen expression in HCT cells transfected with the wild-type human beta2-mu gene is accompanied by the expression of beta2-mu-free HLA class I heavy chains on the cell surface. HCT cells expressing a transfected H-2L(d) gene (HCT-L(d) transfectants) exhibited high levels of H-2L(d) heavy chains on the cell surface, following treatment with human interferon a (IFN-alpha). IFN-treated HCT-L(d) transfectants also expressed high levels of endogenous beta2-g-free HLA class I heavy chains on the cell surface. Incubation of HCT-L(d) transfectants at 26-degrees-C for 24 hours is associated with a striking increase in the surface expression of H-2L(d) heavy chains (comparable to that observed at 37-degrees-C in the presence of IFN), without a concomitant increase in the surface expression of beta2-mu-free HLA class I heavy chains, suggesting that IFN and low temperature act by different mechanisms. These results also indicate that human IFN and H-2L(d) heavy chain can act synergistically in inducing the surface expression of endogenous beta2-mu-free HLA class I heavy chains by HCT cells. The combination of 26-degrees-C incubation and IFN treatment results in the surface expression of beta2-mu-free HLA class I heavy chains in HCT-neo transfectants, suggesting that IFN plays a crucial role in allowing the surface expression of endogenous HLA class I heavy chains in beta2-mu-negative HCT cells.