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- Title
Vaccination with Single Chain Antigen Receptors for Islet-Derived Peptides Presented on I-A<sup>g7</sup> Delays Diabetes in NOD Mice by Inducing Anergy in Self-Reactive T-Cells.
- Authors
Gurr, Werner; Shaw, Margaret; Herzog, Raimund I.; Li, Yanxia; Sherwin, Robert
- Abstract
To develop a vaccination approach for prevention of type 1 diabetes (T1D) that selectively attenuates self-reactive T-cells targeting specific autoantigens, we selected phage-displayed single chain antigen receptor libraries for clones binding to a complex of the NOD classII MHC I-Ag7 and epitopes derived from the islet autoantigen RegII. Libraries were generated from B-cell receptor repertoires of classII-mismatched mice immunized with RegII-pulsed NOD antigen presenting cells or from T-cell receptor repertoires in pancreatic lymph nodes of NOD mice. Both approaches yielded clones recognizing a RegII-derived epitope in the context of I-Ag7, which activated autoreactive CD4+ T-cells. A receptor with different specificity was obtained by converting the BDC2.5 TCR into single chain form. B- but not T-cells from donors vaccinated with the clones transferred protection from diabetes to NOD-SCID recipients if the specificity of the diabetes inducer cell and the single chain receptor were matched. B-cells and antibodies from donors vaccinated with the BDC2.5 single chain receptor induced a state of profound anergy in T-cells of BDC2.5 TCR transgenic NOD recipients while B-cells from donors vaccinated with a single chain receptor specific for I-Ag7 RegII peptide complexes induced only partial non-responsiveness. Vaccination of normal NOD mice with receptors recognizing I-Ag7 RegII peptide complexes or with the BDC2.5 single chain receptor delayed onset of T1D. Thus anti-idiotypic vaccination can be successfully applied to T1D with vaccines either generated from self-reactive T-cell clones or derived from antigen receptor libraries.
- Publication
PLoS ONE, 2013, Vol 8, Issue 7, p1
- ISSN
1932-6203
- Publication type
Academic Journal
- DOI
10.1371/journal.pone.0069464