| First Author | Serre L | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 7 | Pages | 1946-56 |
| PubMed ID | 25884569 | Mgi Jnum | J:229782 |
| Mgi Id | MGI:5754456 | Doi | 10.1002/eji.201445290 |
| Citation | Serre L, et al. (2015) Central tolerance spares the private high-avidity CD4(+) T-cell repertoire specific for an islet antigen in NOD mice. Eur J Immunol 45(7):1946-56 |
| abstractText | Although central tolerance induces the deletion of most autoreactive T cells, some autoreactive T cells escape thymic censorship. Whether potentially harmful autoreactive T cells present distinct TCRalphabeta features remains unclear. Here, we analyzed the TCRalphabeta repertoire of CD4(+) T cells specific for the S100beta protein, an islet antigen associated with type 1 diabetes. We found that diabetes-resistant NOD mice deficient for thymus specific serine protease (TSSP), a protease that impairs class II antigen presentation by thymic stromal cells, were hyporesponsive to the immunodominant S100beta1-15 epitope, as compared to wild-type NOD mice, due to intrathymic negative selection. In both TSSP-deficient and wild-type NOD mice, the TCRalphabeta repertoire of S100beta-specific CD4(+) T cells though diverse showed a specific bias for dominant TCRalpha rearrangements with limited CDR3alpha diversity. These dominant TCRalpha chains were public since they were found in all mice. They were of intermediate- to low-avidity. In contrast, high-avidity T cells expressed unique TCRs specific to each individual (private TCRs) and were only found in wild-type NOD mice. Hence, in NOD mice, the autoreactive CD4(+) T-cell compartment has two major components, a dominant and public low-avidity TCRalpha repertoire and a private high-avidity CD4(+) T-cell repertoire; the latter is deleted by re-enforced negative selection. |
