Evidence for two trans-acting genes regulating HLA class II antigen expression

Previous studies have shown that a trans-acting regulatory factor is required for expression of HLA class II molecules in B-LCL, and that a trans-active factor derived from B-LCL induces de novo synthesis of T-LCL-encoded class II antigens in hybrids of T-LCL and B-LCL. To further examine the genetics of class II antigen regulation, we have now fused two different T-LCL with the class II antigen negative B-LCL 6.1.6, a regulatory mutant that does not synthesize a trans-acting factor necessary for transcription of class II genes. Northern blot analysis and cell surface immunofluorescence studies indicate that the hybrids express class II antigens encoded by both 6.1.6 and T-LCL parent cell lines. Thus, expression of class II antigens in these hybrids is controlled by a minimum of two trans-acting regulatory genes. One of these genes is inactivated in the 6.1.6 mutant and is provided by the T-LCL fusion partner. The second regulatory gene may still be active in 6.1.6, but it alone is insufficient for maintenance of class II antigen expression.