Identification of Natural Regulatory T Cell Epitopes Reveals Convergence on a Dominant Autoantigen

John D. Leonard, Dana C. Gilmore, Thamotharampillai Dileepan, Wioletta I. Nawrocka, Jaime L. Chao, Mary H. Schoenbach, Marc K. Jenkins, Erin J. Adams, Peter A. Savage

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Regulatory T (Treg) cells expressing the transcription factor Foxp3 are critical for the prevention of autoimmunity and the suppression of anti-tumor immunity. The major self-antigens recognized by Treg cells remain undefined, representing a substantial barrier to the understanding of immune regulation. Here, we have identified natural Treg cell ligands in mice. We found that two recurrent Treg cell clones, one prevalent in prostate tumors and the other associated with prostatic autoimmune lesions, recognized distinct non-overlapping MHC-class-II-restricted peptides derived from the same prostate-specific protein. Notably, this protein is frequently targeted by autoantibodies in experimental models of prostatic autoimmunity. On the basis of these findings, we propose a model in which Treg cell responses at peripheral sites converge on those self-proteins that are most susceptible to autoimmune attack, and we suggest that this link could be exploited as a generalizable strategy for identifying the Treg cell antigens relevant to human autoimmunity.

Original languageEnglish (US)
Pages (from-to)107-117.e8
JournalImmunity
Volume47
Issue number1
DOIs
StatePublished - Jul 18 2017

Bibliographical note

Publisher Copyright:
© 2017 Elsevier Inc.

Keywords

  • Aire
  • autoantibodies
  • autoantigens
  • autoimmune regulator
  • autoimmunity
  • immune tolerance
  • prostate cancer
  • regulatory T cells

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