| First Author | Larkin J 3rd | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 4 | Pages | 2149-57 |
| PubMed ID | 18250421 | Mgi Jnum | J:131919 |
| Mgi Id | MGI:3774817 | Doi | 10.4049/jimmunol.180.4.2149 |
| Citation | Larkin J rd, et al. (2008) CD4+CD25+ regulatory T cell repertoire formation shaped by differential presentation of peptides from a self-antigen. J Immunol 180(4):2149-57 |
| abstractText | 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. |
