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T cells specific fo...
T cells specific for post-translational modifications escape intrathymic tolerance induction
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- Raposo, Bruno (author)
- Karolinska Institutet,Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden.;Harvard Med Sch, Dept Microbiol & Immunobiol, 77 Ave Louis Pasteur,NRB 836, Boston, MA 02115 USA.
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- Merky, Patrick (author)
- Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden.
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- Lundqvist, Christina, 1988 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Yamada, Hisakata (author)
- Kyushu Univ, Med Inst Bioregulat, Div Host Def, Fukuoka 8128582, Japan.
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- Urbonaviciute, Vilma (author)
- Karolinska Institutet,Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden.
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- Niaudet, Colin (author)
- Karolinska Inst, Div Vasc Biol, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden.
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- Viljanen, Johan V. (author)
- Uppsala universitet,Organisk kemi
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- Kihlberg, Jan (author)
- Uppsala universitet,Organisk kemi
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- Kyewski, Bruno (author)
- German Canc Res Ctr, Div Dev Immunol, Tumor Immunol Program, D-69120 Heidelberg, Germany.
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- Ekwall, Olov, 1968 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Medicine, Department of Rheumatology and Inflammation Research,Institute of Clinical Sciences, Department of Pediatrics
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- Holmdahl, Rikard (author)
- Karolinska Institutet,Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden.
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- Bäcklund, Johan (author)
- Karolinska Institutet,Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden.
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Karolinska Institutet Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden;Harvard Med Sch, Dept Microbiol & Immunobiol, 77 Ave Louis Pasteur,NRB 836, Boston, MA 02115 USA. (creator_code:org_t)
- 2018-01-24
- 2018
- English.
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Abstract
Subject headings
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- Establishing effective central tolerance requires the promiscuous expression of tissue-restricted antigens by medullary thymic epithelial cells. However, whether central tolerance also extends to post-translationally modified proteins is not clear. Here we show a mouse model of autoimmunity in which disease development is dependent on post-translational modification (PTM) of the tissue-restricted self-antigen collagen type II. T cells specific for the non-modified antigen undergo efficient central tolerance. By contrast, PTM-reactive T cells escape thymic selection, though the PTM variant constitutes the dominant form in the periphery. This finding implies that the PTM protein is absent in the thymus, or present at concentrations insufficient to induce negative selection of developing thymocytes and explains the lower level of tolerance induction against the PTM antigen. As the majority of self-antigens are post-translationally modified, these data raise the possibility that T cells specific for other self-antigens naturally subjected to PTM may escape central tolerance induction by a similar mechanism.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Raposo, Bruno
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Merky, Patrick
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Lundqvist, Chris ...
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Yamada, Hisakata
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Urbonaviciute, V ...
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Niaudet, Colin
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show more...
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Viljanen, Johan ...
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Kihlberg, Jan
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Kyewski, Bruno
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Ekwall, Olov, 19 ...
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Holmdahl, Rikard
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Bäcklund, Johan
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Nature Communica ...
- By the university
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Uppsala University
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Karolinska Institutet
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University of Gothenburg