Differential regulation of constitutive major histocompatibility complex class I expression in T and B lymphocytes.
Major histocompatibility complex (MHC) class I antigens are constitutively expressed yet highly induced by interferon (IFN) during inflammation. We found that not only IFN-induced but also normal basal expression of MHC I required IFN receptors and signal transducer and activator of transcription (STAT)1, providing genetic evidence for continuous IFN signaling. Surprisingly, an IFN-independent requirement for STAT1 was also found, specifically in T lymphocytes, where MHC class I expression was not fully accounted for by IFN signaling. This IFN-independent pathway maintained tyrosine phosphorylation of STAT1 in T but not B lymphocytes even in the absence of IFN receptors. Interestingly, interleukin (IL)-7 selectively activated STAT1 and induced MHC class I in mature T but not B cells. These loss of function studies demonstrate an essential role of endogenous IFN and activated STAT1 for constitutive MHC class I expression in normal mice and define IL-7-dependent but IFN-independent regulation of STAT1 restricted to T lymphocytes.
Lee
C K
CK
Department of Pathology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016, USA.
Gimeno
R
R
Levy
D E
DE
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D007372:Interferons / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D010766:Phosphorylation; D000071156:Promyelocytic Leukemia Protein; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D050794:STAT1 Transcription Factor; D013601:T-Lymphocytes / Q000276:immunology*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C513293:Pml protein, mouse; D000071156:Promyelocytic Leukemia Protein; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D007372:Interferons