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T cell recognition of naturally presented epitopes of self-heat shock protein 70
Authors:Huib de Jong  Eva C Koffeman  Jennifer M Meerding  Rianne C Scholman  Lotte Wieten  Wilco de Jager  Mark Klein  Henny Otten  Femke van Wijk  Ruurd van der Zee  Johannes W J Bijlsma  Femke Broere  Willem van Eden  Berent J Prakken
Institution:1. Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
2. Laboratory of Translational Immunology, Department of Pediatric Immunology, University Medical Center Utrecht, Huispostnummer KE 04.131.1, Postbus 85090, 3508 AB, Utrecht, The Netherlands
3. Department of Infectious Diseases and Immunology, Division of Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
4. Department of Immunology, University Medical Center Utrecht, 3508 GA, Utrecht, The Netherlands
Abstract:Self-reactive T cells have shown to have a potential role as regulators of the immune system preventing or even suppressing autoimmunity. One of the most abundant proteins that can be eluted from human HLA molecules is heat shock protein 70 (HSP70). The aims of the current study are to identify HSP70 epitopes based on published HLA elution studies and to investigate whether T cells from healthy individuals may respond to such self-epitopes. A literature search and subsequent in silico binding prediction based on theoretical MHC binding motifs resulted in the identification of seven HSP70 epitopes. PBMCs of healthy controls proliferated after incubation with two of the seven peptides (H167 and H290). Furthermore H161, H290, and H443 induced CD69 expression or production of cytokines IFNγ or TNFα in healthy controls. The identification of these naturally presented epitopes and the response they elicit in the normal immune system make them potential candidates to study during inflammatory conditions as well as in autoimmune diseases.
Keywords:Heat shock protein 70  HSP70  Naturally processed T cell epitopes  Human HSP70 peptides  Autoreactive T cells
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