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Heat Shock Up-Regulates lmp2 and lmp7 and Enhances Presentation of Immunoproteasome-Dependent Epitopes¹

Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030

The heat shock response is a canonical regulatory pathway by which cellular stressors such as heat and oxidative stress alter the expression of stress-responsive genes. Some of these stress-responsive genes (heat shock proteins and MHC class I (MHC I)-related chains) play a significant role in the immune system. In this study, we have investigated the impact of stimulating the heat shock response on genes involved in the MHC I presentation pathway. We report that two inducible subunits of the proteasome, lmp2 and lmp7, are transcriptionally up-regulated by heat shock in cells of mouse and human origin. Furthermore, heat-shocked cells show enhanced presentation of the immunoproteasome-dependent MHC I antigenic epitopes NP^118–126 of lymphocytic choriomeningitis virus and E1B^192–200 of adenovirus, but not immunoproteasome-independent epitopes such as tumor Ag AH1 and SV40 large T Ag epitope II^223–231. These findings show a novel immunological sequel to the cellular response to stress that may play a key role during fever or other homeostatic perturbations.

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.

¹ This work was supported by National Institutes of Health Medical Scientist Training Program Grant (to M.K.C.), National Institutes of Health National Cancer Institute Grants (to A.M.) and (to P.K.S.), and by a sponsored research agreement with Antigenics.

² Address correspondence and reprint requests to Dr. Margaret K. Callahan, Center for Immunotherapy, University of Connecticut, Farmington, CT 06030-1601. E-mail address: marcallahan{at}studentuchc.edu

³ Abbreviations used in this paper: hsp, heat shock protein; LCMV, lymphocyte choriomeningitis virus; NP, nucleoprotein; qPCR, quantitative PCR.

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