Epitopes described in "Detection of an autoreactive T-cell population within the polyclonal repertoire that undergoes distinct autoimmune regulator (Aire)-mediated selection."

Article Authors:Ruth T Taniguchi; Jason J DeVoss; James J Moon; John Sidney; Alessandro Sette; Marc K Jenkins; Mark S Anderson
Article Title:Detection of an autoreactive T-cell population within the polyclonal repertoire that undergoes distinct autoimmune regulator (Aire)-mediated selection.
Reference Detail
Reference ID:1024175
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.
Affiliations:Diabetes Center, University of California, San Francisco, CA 94143, USA.
Reference Type:Literature
PubMed ID:22552229
Journal:Proc Natl Acad Sci U S A
Journal Volume:109
Article Pages:7847-52
Journal ISSN:0027-8424
Article Chemical List:APECED protein;Eye Proteins;Retinol-Binding Proteins;Transcription Factors;interstitial retinol-binding protein
Article MeSH List:Animals; Antigen-Presenting Cells(immunology; metabolism); Clonal Deletion(genetics; immunology); Eye Proteins(immunology; metabolism); Immunization; Mice; Mice, Inbred C57BL; Mice, Knockout; Retinol-Binding Proteins(immunology; metabolism); Statistics, Nonparametric; T-Lymphocytes(immunology; metabolism); Thymus Gland(cytology; immunology); Transcription Factors(genetics; immunology); Uveitis(immunology; pathology)
Curation Last Updated:2015-07-30 20:45:46