| First Author | Serreze DV | Year | 2007 |
| Journal | Ann N Y Acad Sci | Volume | 1103 |
| Pages | 103-11 | PubMed ID | 17376821 |
| Mgi Jnum | J:123948 | Mgi Id | MGI:3720201 |
| Doi | 10.1196/annals.1394.019 | Citation | Serreze DV, et al. (2007) 'Humanized' HLA transgenic NOD mice to identify pancreatic beta cell autoantigens of potential clinical relevance to type 1 diabetes. Ann N Y Acad Sci 1103:103-11 |
| abstractText | The mechanistic basis by which the H2(g7) major histocompatibility complex (MHC) provides the primary risk factor for the development of T cell-mediated autoimmune type 1 diabetes (T1D) in non-obese diabetic (NOD) mice involves contributions not only from the unusual A(g7) class II molecule, but also from the more common K(d) and/or D(b) class I variants it encodes. Similarly, transgenic studies in NOD mice have confirmed the possibility first suggested in association studies that in the proper genetic context the common human HLA-A2.1 class I variant can mediate diabetogenic CD8 T cell responses. T1D continues to develop in a further refined NOD stock that expresses human HLA-A2.1, but no murine class I molecules (designated NOD.beta2m-.HHD). Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is an important antigenic target of diabetogenic CD8 cells in standard NOD mice. Three IGRP-derived peptides have also been identified that are presented by human HLA-A2.1 molecules to diabetogenic CD8 T cells in NOD.beta2m-.HHD mice. At least one of these IGRP peptides (265-273) can also be the target of autoreactive CD8 T cells in HLA-A2.1-expressing human T1D patients. Studies are currently under way to determine whether HLA-A2.1-restricted IGRP peptides can be used in a tolerance-inducing protocol that inhibits T1D development in NOD. beta2m-.HHD mice. If so, this knowledge could ultimately lead to the development of a similar T1D prevention protocol in humans. |
