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| Article Authors: | Joseph Larkin 3rd; Andrew L Rankin; Cristina Cozzo Picca; Michael P Riley; Scott A Jenks; Andrea J Sant; Andrew J Caton |
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| Article Title: | CD4+CD25+ regulatory T cell repertoire formation shaped by differential presentation of peptides from a self-antigen. |
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| Reference ID: | 1021298 |
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| Abstract: | We have used TCR transgenic mice directed to different MHC class II-restricted determinants from the influenza virus hemagglutinin (HA) to analyze how specificity for self-peptides can shape CD4+CD25+ regulatory T (Treg) cell formation. We show that substantial increases in the number of CD4+CD25+ Treg cells can occur when an autoreactive TCR directed to a major I-E(d)-restricted determinant from HA develops in mice expressing HA as a self-Ag, and that the efficiency of this process is largely unaffected by the ability to coexpress additional TCR alpha-chains. This increased formation of CD4+CD25+ Treg cells in the presence of the self-peptide argues against models that postulate selective survival rather than induced formation as mechanisms of CD4+CD25+ Treg cell formation. In contrast, T cells bearing a TCR directed to a major I-A(d)-restricted determinant from HA underwent little or no selection to become CD4+CD25+ Treg cells in mice expressing HA as a self-Ag, correlating with inefficient processing and presentation of the peptide from the neo-self-HA polypeptide. These findings show that interactions with a self-peptide can induce thymocytes to differentiate along a pathway to become CD4+CD25+ Treg cells, and that peptide editing by DM molecules may help bias the CD4+CD25+ Treg cell repertoire away from self-peptides that associate weakly with MHC class II molecules. |
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| Affiliations: | The Wistar Institute, Philadelphia, PA 19104, USA. |
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| Date: | 2008 |
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| Reference Type: | Literature |
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| PubMed ID: | 18250421 |
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| Journal: | J Immunol |
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| Journal Volume: | 180 |
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| Article Pages: | 2149-57 |
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| Journal ISSN: | 0022-1767 |
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| Article Chemical List: | Autoantigens;Hemagglutinins, Viral;Peptides;Receptors, Antigen, T-Cell |
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| Article MeSH List: | Animals; Antigen Presentation(genetics; immunology); Autoantigens(biosynthesis; genetics; immunology; metabolism); Cell Differentiation(genetics; immunology); Hemagglutinins, Viral(biosynthesis; genetics; immunology; metabolism); Influenza A virus(immunology); L Cells (Cell Line); Mice; Mice, Inbred BALB C; Mice, Knockout; Mice, Transgenic; Peptides(immunology; metabolism); Receptors, Antigen, T-Cell(genetics); T-Lymphocytes, Regulatory(cytology; immunology; metabolism) |
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| Curation Last Updated: | 2011-04-04 20:01:15 |
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