Abstract
INSULIN-dependent diabetes mellitus is characterized by the infiltration of lymphocytes into the islets of Langerhans of the pancreas (insulitis) followed by destruction of insulin-secreting β-cells leading to overt diabetes1–5. The best model for the disease is the non-obese diabetic (NOD) mouse6,7. Two unusual features of the class II major histocompatibility complex (MHC)8,9 of the NOD mouse are the absence of I-E9 and the presence of unique I-A molecules (I-ANOD)10, in which aspartic acid at position 57 of the β-chain is replaced by serine. This feature is also found in the HLA-DQ chain of many Caucasians with insulin-dependent diabetes mellitus11–13. We have previously reported that the expression of I-E prevents the development of insulitis in NOD mouse14,15. Here we report that the expression of I-Ak (AαkAβk) in transgenic NOD mice can also prevent insulitis, and that this protection is seen not only when the I-A β-chain has aspartic acid as residue 57, but also when this residue is serine. These results show that the single amino-acid substitution at position 57 of the I-A β-chain from aspartic acid to serine is not sufficient for the development of the disease.
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Miyazaki, T., Uno, M., Uehira, M. et al. Direct evidence for the contribution of the unique I-ANOD to the development of insulitis in non-obese diabetic mice. Nature 345, 722–724 (1990). https://doi.org/10.1038/345722a0
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DOI: https://doi.org/10.1038/345722a0
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