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Immunity. 2017 Jul 18;47(1):107-117.e8. doi: 10.1016/j.immuni.2017.06.015. Epub 2017 Jul 11.

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

Author information

1
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
2
Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
3
Department of Microbiology and Immunology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
4
Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA. Electronic address: ejadams@uchicago.edu.
5
Department of Pathology, University of Chicago, Chicago, IL 60637, USA. Electronic address: psavage@bsd.uchicago.edu.

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.

KEYWORDS:

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

PMID:
28709804
PMCID:
PMC5562039
DOI:
10.1016/j.immuni.2017.06.015
[Indexed for MEDLINE]
Free PMC Article

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