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| Article Authors: | Ruth T Taniguchi; Jason J Devoss; James J Moon; John Sidney; Alessandro Sette; Marc K Jenkins; Mark S Anderson |
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| Article Title: | Detection of an autoreactive T-cell population within the polyclonal repertoire that undergoes distinct autoimmune regulator (Aire)-mediated selection. |
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| Reference ID: | 1024175 |
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| Abstract: | The autoimmune regulator (Aire) plays a critical role in central tolerance by promoting the display of tissue-specific antigens in the thymus. To study the influence of Aire on thymic selection in a physiological setting, we used tetramer reagents to detect autoreactive T cells specific for the Aire-dependent tissue-specific antigen interphotoreceptor retinoid-binding protein (IRBP), in the polyclonal repertoire. Two class II tetramer reagents were designed to identify T cells specific for two different peptide epitopes of IRBP. Analyses of the polyclonal T-cell repertoire showed a high frequency of activated T cells specific for both IRBP tetramers in Aire(-/-) mice, but not in Aire(+/+) mice. Surprisingly, although one tetramer-binding T-cell population was efficiently deleted in the thymus in an Aire-dependent manner, the second tetramer-binding population was not deleted and could be detected in both the Aire(-/-) and Aire(+/+) T-cell repertoires. We found that Aire-dependent thymic deletion of IRBP-specific T cells relies on intercellular transfer of IRBP between thymic stroma and bone marrow-derived antigen-presenting cells. Furthermore, our data suggest that Aire-mediated deletion relies not only on thymic expression of IRBP, but also on proper antigen processing and presentation of IRBP by thymic antigen-presenting cells. |
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| Affiliations: | Diabetes Center, University of California, San Francisco, CA 94143. |
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| Date: | 2012 |
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| Reference Type: | Literature |
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| PubMed ID: | 22552229 |
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| Journal: | Proc Natl Acad Sci U S A |
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| Journal Volume: | 109 |
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| Article Pages: | 7847-52 |
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| Journal ISSN: | 1091-6490 |
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| Curation Last Updated: | 2012-06-20 20:01:11 |
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