Original Article

Differential Regulation of Constitutive Major Histocompatibility Complex Class I Expression in T and B Lymphocytes

Correspondence to: David E. Levy, Dept. of Pathology, New York University School of Medicine, 550 First Ave., New York, NY 10016. Tel:212-263-8192 Fax:212-263-8211 E-mail:levyd01{at}med.nyu.edu.

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.

Key Words: interferon, STAT1, interleukin-7, gene regulation, tyrosine phosphorylation

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