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Interferon‐γ‐Induced MHC Class I Expression and Defects in Jak/Stat Signalling in Methylcholanthrene‐Induced Sarcomas
Author(s) -
SVANE I. M.,
ENGEL A.M.,
NIELSEN M.,
WERDELIN O.
Publication year - 1997
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1997.d01-141.x
Subject(s) - stat1 , major histocompatibility complex , biology , cancer research , phosphorylation , mhc class i , interferon , mhc class ii , signal transduction , cell culture , methylcholanthrene , tyrosine phosphorylation , interferon gamma , microbiology and biotechnology , immunology , immune system , carcinogen , genetics
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 K d , D d and L d was measured by fluorescence‐activated cell sorter analysis. All but three of the 78 tumour lines up‐regulated K d , D d and L d 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.