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

Publication date: Available online 11 July 2017
Source:Immunity
Author(s): 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
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.

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Teaser

The endogenous antigens recognized by thymus-derived Treg cells have remained largely undefined. Leonard et al. identify natural Treg cell ligands in mice, demonstrating that two recurrent Treg cell clones recognize distinct non-overlapping peptides derived from a single prostate-specific protein.


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