A peptide of glutamic acid decarboxylase 65 can recruit and expand a diabetogenic T cell clone, BDC2.5, in the pancreas

Dai, YD; Jensen, KP; Lehuen, A; Masteller, EL; Bluestone, JA; Wilson, DB; Sercarz, EE

Author(s): Dai, YD; Jensen, KP; Lehuen, A; Masteller, EL; Bluestone, JA; Wilson, DB; Sercarz, EE;
Details: Publication Year 2005-09-15,Volume 175,Issue #6,Page 3621-3627
Journal Title: JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: Self peptide-MHC ligands create and maintain the mature T cell repertoire by positive selection in the thymus and by homeostatic proliferation in the periphery. A low affinity/avidity interaction among T cells, self peptides, and MHC molecules has been suggested for these events, but it remains unknown whether or how this self-interaction is involved in tolerance and/or autoimmunity. Several lines of evidence implicate the glutamic acid decarboxylase 65 (GAD-65) peptide, p524-543, as a specific, possibly low affinity, stimulus for the spontaneously arising, diabetogenic T cell clone BDC2.5. Interestingly, BDC2.5 T cells, which normally are unresponsive to p524-543 stimulation, react to the peptide when provided with splenic APC obtained from mice immunized with the same peptide, p524-543, but not, for example, with hen egg white lysozyme. Immunization with p524-543 increases the susceptibility of the NOD mice to type 1 diabetes induced by the adoptive transfer of BDC2.5 T cells. In addition, very few CFSE-labeled BDC2.5 T cells divide in the recipient's pancreas after transfer into a transgenic mouse that overexpresses GAD-65 in B cells, whereas they divide vigorously in the pancreas of normal NOD recipients. A special relationship between the BDC2.5 clone and the GAD-65 molecule is further demonstrated by generation of a double-transgenic mouse line carrying both the BDC2.5 TCR and GAD-65 transgenes, in which a significant reduction of BDC2.5 cells in the pancreas has been observed, presumably due to tolerance induction. These data suggest that unique and/or altered processing of self Ags may play an essential role in the development and expansion of autoreactive T cells.
Publisher: AMER ASSOC IMMUNOLOGISTS
Keywords: NONOBESE DIABETIC MICE; ANTIGEN-PRESENTING CELLS; NOD MICE; B-LYMPHOCYTES; IDENTIFICATION; DETERMINANTS; AUTOANTIGEN; RESPONSES; EPITOPES; PROLIFERATION
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Creation Date: 2005-09-15 12:00:00