| First Author | DiPaolo RJ | Year | 2001 |
| Journal | Eur J Immunol | Volume | 31 |
| Issue | 12 | Pages | 3453-9 |
| PubMed ID | 11745364 | Mgi Jnum | J:73354 |
| Mgi Id | MGI:2155000 | Doi | 10.1002/1521-4141(200112)31:12<3453::aid-immu3453>3.0.co;2-h |
| Citation | DiPaolo RJ, et al. (2001) The level of peptide-MHC complex determines the susceptibility to autoimmune diabetes: studies in HEL transgenic mice. Eur J Immunol 31(12):3453-9 |
| abstractText | We report a mouse model for the spontaneous development of autoimmune diabetes: the 3A9 T cell receptor (TCR) transgenic mouse, which contains T cells that recognize the 52 - 61 family of hen egg-white lysozyme (HEL) peptides in the context of MHC class II I-A(k) molecules, was bred to the ILK3 mouse, that expresses HEL protein via the rat insulin promoter (RIP). Despite partial tolerance of 3A9 T cells in ILK3 mice, spontaneous diabetes developed in 64 % of 3A9xILK3 mice by 20 weeks of age. We provide evidence that APC from peri-pancreatic nodes have a large contentof peptide-MHC complex and stimulate 3A9 T cells. We also report that cross presentation of HEL from beta cells to APC is 26-fold more efficient than presentation of soluble HEL. We previously reported on a biochemical margin of safety, based on the observation that activation of naive 3A9 T cells required 100-fold more peptide-MHC complexes than required for deletion of 3A9 thymocytes. We speculate that the high local density of autologous peptide-MHC complexes can be a determining factor that leads to the activation of autoreactive CD4 T cells and, consequently, to the developmentof autoimmunity. |
