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  • Raposo, BrunoKarolinska 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. (author)

T cells specific for post-translational modifications escape intrathymic tolerance induction

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • 2018-01-24
  • NATURE PUBLISHING GROUP,2018
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-343795
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-343795URI
  • https://doi.org/10.1038/s41467-017-02763-yDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:137481430URI
  • https://gup.ub.gu.se/publication/264111URI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 and genre

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  • Merky, PatrickKarolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden. (author)
  • Lundqvist, Christina,1988Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xluchl (author)
  • Yamada, HisakataKyushu Univ, Med Inst Bioregulat, Div Host Def, Fukuoka 8128582, Japan. (author)
  • Urbonaviciute, VilmaKarolinska Institutet,Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden. (author)
  • Niaudet, ColinKarolinska Inst, Div Vasc Biol, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden. (author)
  • Viljanen, Johan V.Uppsala universitet,Organisk kemi(Swepub:uu)johvi609 (author)
  • Kihlberg, JanUppsala universitet,Organisk kemi(Swepub:uu)janki643 (author)
  • Kyewski, BrunoGerman Canc Res Ctr, Div Dev Immunol, Tumor Immunol Program, D-69120 Heidelberg, Germany. (author)
  • Ekwall, Olov,1968Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Clinical Sciences, Department of Pediatrics,Institute of Medicine, Department of Rheumatology and Inflammation Research(Swepub:gu)xekwol (author)
  • Holmdahl, RikardKarolinska Institutet,Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden. (author)
  • Bäcklund, JohanKarolinska Institutet,Karolinska Inst, Sect Med Inflammat Res, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden. (author)
  • Karolinska InstitutetKarolinska 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)

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  • In:Nature Communications: NATURE PUBLISHING GROUP92041-1723

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