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

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© The Rockefeller University Press, 0022-1007/1999/11/1451/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 10, November 15, 1999 1451-1464

Original Article

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

Chien-Kuo Lee^a, Ramon Gimeno^a, and David E. Levy^a

^a Department of Pathology and Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, New York 10016
Dept. of Pathology, New York University School of Medicine, 550 First Ave., New York, NY 10016.212-263-8211212-263-8192

levyd01{at}med.nyu.edu

Major histocompatibility complex (MHC) class I antigens areconstitutively expressed yet highly induced by interferon (IFN)during inflammation. We found that not only IFN-induced butalso normal basal expression of MHC I required IFN receptorsand 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, specificallyin T lymphocytes, where MHC class I expression was not fullyaccounted for by IFN signaling. This IFN-independent pathwaymaintained tyrosine phosphorylation of STAT1 in T but not Blymphocytes even in the absence of IFN receptors. Interestingly,interleukin (IL)-7 selectively activated STAT1 and induced MHCclass I in mature T but not B cells. These loss of functionstudies demonstrate an essential role of endogenous IFN andactivated STAT1 for constitutive MHC class I expression in normalmice and define IL-7–dependent but IFN-independent regulationof STAT1 restricted to T lymphocytes.

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

1used in this paper: BMT, bone marrow transplantation; DN, double-negative;DP, double-positive; EMSA, electrophoretic mobility gel shift;GFP, green fluorescent protein; ICS, IFN consensus sequence;IRF, IFN regulatory factor; NF, nuclear factor; PML, promyelocyticleukemia; SP, single-positive; STAT, signal transducer and activatorof transcription; TAP, transporter associated with antigen processing

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