Interferon‐γ‐Induced MHC Class I Expression and Defects in Jak/Stat Signalling in Methylcholanthrene‐Induced Sarcomas

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Abstract
Seventy‐eight uncloned tumour cell lines, each established from a primary sarcoma induced with methylcholanthrene in immunocompetent nu/+ BALB/c and C.B.‐17 mice or in immunodeficient nu/nu BALB/c and severe combined immunodeficient (SCID) mice, were examined for sensitivity to interferon‐γ (IFN‐γ) as measured by tumour cell augmentation of major histocompatibility complex (MHC) class I expression. The tumour cells were cultured with IFN‐γ and their expression of Kd, Dd and Ld was measured by fluorescence‐activated cell sorter analysis. All but three of the 78 tumour lines up‐regulated Kd, Dd and Ld to a variable degree in response to IFN‐γ, indicating that IFN‐γ resistance is not a common property of these sarcomas. The tumour cell lines varied greatly in their MHC class I expression before as well as after IFN‐γ stimulation. There was a tendency towards a higher MHC expression after IFN‐γ stimulation in tumour lines from immunocompetent mice compared to immunodeficient mice, but no common maximum MHC class I expression level was found for the 78 tumour cell lines. Three of the tumour lines, all from immunodeficient mice, completely failed to respond to IFN‐γ by up‐regulating MHC class I expression. The same three also displayed absence of IFN‐γ‐induced Stat1β tyrosine phosphorylation and low Stat1α tyrosine phosphorylation, indicating a defect in the signal transduction pathway affecting phosphorylation of Stat1. These findings strongly suggest a link between defects in Stat1 phosphorylation and the failure to up‐regulate MHC class I. In all tumour lines tested, the Stat1 Western blotting revealed a 78 kDa protein (p78) not previously described.
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