Heat shock up-regulates lmp2 and lmp7 and enhances presentation of immunoproteasome-dependent epitopes.
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.
Callahan
Margaret K
MK
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030, USA. marcallahan@studentuchc.edu
Wohlfert
Elizabeth A
EA
Ménoret
Antoine
A
Srivastava
Pramod K
PK
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003110:Colonic Neoplasms; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000276:immunology*; D000939:Epitopes / Q000502:physiology*; D005354:Fibrosarcoma; D018882:Heat Stress Disorders / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D006801:Humans; D007109:Immunity / Q000502:physiology; D051379:Mice; D009097:Multienzyme Complexes / Q000096:biosynthesis / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology / Q000502:physiology*
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex