| First Author | Mohan JF | Year | 2011 |
| Journal | J Exp Med | Volume | 208 |
| Issue | 12 | Pages | 2375-83 |
| PubMed ID | 22065673 | Mgi Jnum | J:178627 |
| Mgi Id | MGI:5299380 | Doi | 10.1084/jem.20111502 |
| Citation | Mohan JF, et al. (2011) Register shifting of an insulin peptide-MHC complex allows diabetogenic T cells to escape thymic deletion. J Exp Med 208(12):2375-83 |
| abstractText | In nonobese diabetic (NOD) mice, two sets of autoreactive CD4(+) T cells recognize the B:9-23 segment of the insulin B chain. One set, type A, recognizes insulin presented by antigen-presenting cells (APCs). These T cells are highly deleted in the thymus. The second set, type B, does not recognize insulin protein but reacts with soluble B chain peptide. This set is not deleted in the thymus but is activated in the islets of Langerhans. In this study, we examine the specificity of these two types of T cells. The protein-reactive set recognizes the stretch of residues 13-21 of the insulin B chain. The set reactive to peptide only recognizes the stretch from residues 12-20. A single amino acid shift of the B chain peptide bound to I-A(g7) determines whether T cells recognize peptides generated by the processing of insulin, and consequently their escape from thymic purging. Biochemical experiments indicate that peptides bound in the 13-21 register interact more favorably with I-A(g7) than peptides that bind in the 12-20 register. Thus, self-reactive T cells can become pathogenic in the target organ where high concentrations of antigen and/or differences in intracellular processing present peptides in registers distinct from those found in the thymus. |
