Epitopes described in "CD4+CD25+ regulatory T cell repertoire formation shaped by differential presentation of peptides from a self-antigen."

Article Authors:Joseph Larkin 3rd; Andrew L Rankin; Cristina Cozzo Picca; Michael P Riley; Scott A Jenks; Andrea J Sant; Andrew J Caton
Article Title:CD4+CD25+ regulatory T cell repertoire formation shaped by differential presentation of peptides from a self-antigen.
Reference Detail
Reference ID:1021298
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.
Affiliations:The Wistar Institute, Philadelphia, PA 19104, USA.
Reference Type:Literature
PubMed ID:18250421
Journal:J Immunol
Journal Volume:180
Article Pages:2149-57
Journal ISSN:0022-1767
Article Chemical List:Autoantigens;Hemagglutinins, Viral;Peptides;Receptors, Antigen, T-Cell
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)
Curation Last Updated:2015-07-30 20:38:41