| First Author | Toivonen R | Year | 2015 |
| Journal | Mol Immunol | Volume | 64 |
| Issue | 1 | Pages | 127-35 |
| PubMed ID | 25480393 | Mgi Jnum | J:223261 |
| Mgi Id | MGI:5648603 | Doi | 10.1016/j.molimm.2014.11.009 |
| Citation | Toivonen R, et al. (2015) Islet-associated T-cell receptor-beta CDR sequence repertoire in prediabetic NOD mice reveals antigen-driven T-cell expansion and shared usage of VbetaJbeta TCR chains. Mol Immunol 64(1):127-35 |
| abstractText | Autoimmune destruction of pancreatic islets in the nonobese diabetic (NOD) mouse is driven by T cells recognizing various autoantigens mostly in insulin-producing beta-cells. To investigate if T-cell accumulation in islets during early insulitis is clonally predetermined, we compared the complementarity determining regions (CDR3) of T-cell receptor (TCR)beta-chains present in islet-infiltrating T cells in young prediabetic NOD mice. High-throughput sequencing of TCRbeta-chain DNA extracted from islets of 7-wk old NOD mice revealed a biased TCRbeta-chain repertoire in all mice, as a restricted number of clones (17-36 clones) was highly overrepresented and made over 20% of total islet repertoire in each mouse. Among these clones, various Vbeta and Jbeta families were present but certain VbetaJbeta combinations such as TRBV19-0-TRBJ2-7 and TRBV13-3-TRBJ2-5 were highly shared between individual mice. On TCRbeta-chain CDR sequence level, many islet clones (72-146) were shared between at least two individual mice. None of them was among expanded clones in both, suggesting considerable stochasticity in the interactions between TCR and peptide-MHC, even with a limited range of autoantigens. A comparison of islet-CDR3-sequences with CRD-sequences from other tissues revealed clonal overlap with pancreatic lymph node and gut, but these repertoires did not overlap together. Our results suggest that antigen-specific T cells are expanded in pancreatic lymph node and islets, but different specificities expand in individual mice. Some islet-infiltrating T-cell specificities may have a distinct origin shared with gut-infiltrating T cells. |
