T cell receptor assessment in autoimmune disease requires access to the most adjacent immunologically active organ

Bergithe E. Oftedal, Brita Ardesjö Lundgren, David Hamm, Poh Yi Gan, Stephen R. Holdsworth, Christopher N Hahn, Andreas W. Schreiber, Hamish Steele Scott

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Next generation sequencing of T and B cell receptors is emerging as a valuable and effective method to diagnose and monitor hematopoietic malignancies. So far, this approach has not been fully explored in regard to autoimmune diseases. T cells develop in the thymus where they undergo positive and negative selection, and the autoimmune regulator (Aire) is central in the establishment of immunological tolerance. Loss of Aire leads to severe multiorgan autoimmune disease with infiltration of autoreactive T cells in affected organs. Here, we have utilized next generation sequencing technology to investigate the T cell receptor repertoire in autoimmunity induced by immunization of mice with a self-antigen, myeloperoxidase. By investigating the T cell receptor repertoire in peripheral blood, spleen and lumbar lymph nodes from naïve and immunized Aire −/− mice and wild type littermates, changes in the usage of V and J genes were evident. Our results identify TCR clonotypes which could be potential targets for immune therapy. Also, Aire −/− autoimmunity is driven by a variety of autoantigens where the autoimmune response is highly polyclonal, and access to the most adjacent immunologically active tissue is required to identify T cell receptor sequences that are potentially unique to the antigen in Aire−/− immunized mice.

Original languageEnglish
Pages (from-to)24-33
Number of pages10
JournalJournal of Autoimmunity
Volume81
DOIs
Publication statusPublished - 1 Jul 2017

Keywords

  • Autoimmune regulator
  • Next generation sequencing
  • T cell receptor repertoire

Cite this

Oftedal, Bergithe E. ; Ardesjö Lundgren, Brita ; Hamm, David ; Gan, Poh Yi ; Holdsworth, Stephen R. ; Hahn, Christopher N ; Schreiber, Andreas W. ; Scott, Hamish Steele. / T cell receptor assessment in autoimmune disease requires access to the most adjacent immunologically active organ. In: Journal of Autoimmunity. 2017 ; Vol. 81. pp. 24-33.
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abstract = "Next generation sequencing of T and B cell receptors is emerging as a valuable and effective method to diagnose and monitor hematopoietic malignancies. So far, this approach has not been fully explored in regard to autoimmune diseases. T cells develop in the thymus where they undergo positive and negative selection, and the autoimmune regulator (Aire) is central in the establishment of immunological tolerance. Loss of Aire leads to severe multiorgan autoimmune disease with infiltration of autoreactive T cells in affected organs. Here, we have utilized next generation sequencing technology to investigate the T cell receptor repertoire in autoimmunity induced by immunization of mice with a self-antigen, myeloperoxidase. By investigating the T cell receptor repertoire in peripheral blood, spleen and lumbar lymph nodes from na{\"i}ve and immunized Aire −/− mice and wild type littermates, changes in the usage of V and J genes were evident. Our results identify TCR clonotypes which could be potential targets for immune therapy. Also, Aire −/− autoimmunity is driven by a variety of autoantigens where the autoimmune response is highly polyclonal, and access to the most adjacent immunologically active tissue is required to identify T cell receptor sequences that are potentially unique to the antigen in Aire−/− immunized mice.",
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T cell receptor assessment in autoimmune disease requires access to the most adjacent immunologically active organ. / Oftedal, Bergithe E.; Ardesjö Lundgren, Brita; Hamm, David; Gan, Poh Yi; Holdsworth, Stephen R.; Hahn, Christopher N; Schreiber, Andreas W.; Scott, Hamish Steele.

In: Journal of Autoimmunity, Vol. 81, 01.07.2017, p. 24-33.

Research output: Contribution to journalArticleResearchpeer-review

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