Identification of Natural Regulatory T Cell Epitopes Reveals Convergence on a Dominant Autoantigen.
Immunity
; 47(1): 107-117.e8, 2017 07 18.
Article
em En
| MEDLINE
| ID: mdl-28709804
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.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Autoantígenos
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Timo
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Linfócitos T Reguladores
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Epitopos de Linfócito T
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article