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J. Biol. Chem., Vol. 280, Issue 25, 24277-24285, June 24, 2005

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Distinct Transcriptional Control Mechanisms of Killer Immunoglobulin-like Receptors in Natural Killer (NK) and in T Cells^*

Jing Xu, Abbe N. Vallejo, Yong Jiang¶, Cornelia M. Weyand, and Jörg J. Goronzy||

From the Department of Medicine, Lowance Center for Human Immunology, Emory School of Medicine, Atlanta, Georgia 30322, the Departments of Pediatrics and Immunology, University of Pittsburgh School of Medicine, Children's Hospital Rangos Research Center, Pittsburgh, Pennsylvania 15213, and the ^¶Division of Physiological Imaging Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905

Killer immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) cells and by subsets of CD4⁺ and CD8⁺ T cells, which are therefore thought to be subject to similar regulatory mechanisms. Here, we show that the transcriptional machinery to express KIR is limited to NK and T cells; however, the KIR transcriptional control differs between these two types of lymphocytes. T cells selectively express transcriptional activators binding to positions -52 to -61 of the KIR promoter, whereas an AML site around position-98 is relevant for transcription in NK cells. Although KIR expression is restricted to subsets of memory T cells, our studies demonstrate that transcriptional activators for KIRs are not acquired during T cell differentiation but are already present in naïve T cells, suggesting a basic role of KIRs in T cell biology. We suggest that the regulated expression of KIRs in T cells profoundly influences peripheral tolerance and antigen-specific immune responses.

Received for publication, January 20, 2005 , and in revised form, April 28, 2005.

We dedicate this article to Oliver Li, surviving son of Dr. Jing Xu.

^* This work was supported by National Institutes of Health Grants AR42527, AR41974, AG22379, and AG15043. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Deceased February 19, 2004.

^|| To whom correspondence should be addressed: Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University School of Medicine, Rm. 1003, Woodruff Memorial Research Bldg., 101 Woodruff Circle, Atlanta, GA 30322. Tel.: 404-727-7310; Fax: 404-727-7371; E-mail: jgoronz{at}emory.edu.

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