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Protective influence of mhc genes on diabetes in a tcr transgenic mouse model


In the NOD mouse, a valuable model for human IDDM, the diabetes susceptibility is linked to MHC II genes, but the mechanism(s) of influence at the T cell level are not yet clear. Using the established BDC2.5 TCR transgenic mouse line and making appropriate crosses into the B6, NOD and B6.H-2g7 background, 4 lines of mice could be obtained with homo- and heterozygous expression of the NOD MEIC H-2g7 or B6 MHC H-2b in the NOD or B6 background, respectively.
The aim of this study is to investigate the protection mechanism(s) of the non-NOD MHC II Ab molecule on insulitis and IDDM. At first, two mice lines carrying knock-out alleles should be generates to confirm the direct role of the Ab molecule and to eliminate the contribution of non-transgenic TCRs. Furthermore, the T cells from the different mouse lines and the expression of MHC of MHC molecules in splenic antigen presenting cells (APSs)will be compared. Finally, the ability for these APSs to stimulate T cell proliferation and especially the influence on the Th1/Th2 balance should be investigated.

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