Ia antigens and associated invariant chain are induced simultaneously in lines of T-dependent mast cells by recombinant interferon-gamma.

Metabolic labeling and immunoprecipitation with monoclonal antibodies, showed that lines of T-dependent mast cells (P cells) that were cultured in the absence of interferon-gamma (IFN-gamma) did not synthesize detectable amounts of Ia antigens or the invariant chain (Ii). After exposure for 24 hr to IFN-gamma produced from the cloned Mu IFN-gamma gene, P cells synthesized large amounts of Ia alpha- and beta-chains and of the invariant chain. The I-A and I-E antigens of these T-dependent mast cells were indistinguishable from those of B cells in terms of the binding of a panel of monoclonal antibodies and in terms of their structure and that of associated molecules as analyzed in two-dimensional gels. The effect of IFN-gamma on Ii synthesis in P cells was not due merely to inhibition of proliferation, as is the case with certain B cell lines, because treatment of P cells with mitomycin C did not induce the invariant chain. Variant lines of P cells that did not respond to IFN-gamma with the synthesis of Ia antigens, but only the enhanced expression of H-2K, H-2D, and H-2L antigens, also failed to synthesize Ii chain. Experiments using three tumor lines related to B lymphocytes, however, indicated that in these cells IFN-gamma could enhance the synthesis of Ii in the absence of Ia antigens. Whereas Ii chain may be essential for Ia expression, Ii chain may have further functions and in some lines can be regulated independently by IFN-gamma in the absence of Ia antigen expression.