Peptides From Common Viral and Bacterial Pathogens Can Efficiently Activate Diabetogenic T-Cells
- 1Department of Immunology, The Scripps Research Institute, La Jolla, California
- 2Department of Immunochemistry, Torrey Pines Institute for Molecular Studies, San Diego, California
- Address correspondence and reprint requests to Clemencia Pinilla, PhD, Torrey Pines Institute for Molecular Studies, 3550 General Atomics Ct., San Diego, CA 92121. E-mail: cpinilla{at}tpims.org
Abstract
Cross-reactivity between an autoantigen and unknown microbial epitopes has been proposed as a molecular mechanism involved in the development of insulin-dependent diabetes (type 1 diabetes). Type 1 diabetes is an autoimmune disease that occurs in humans and the nonobese diabetic (NOD) mouse. BDC2.5 is an islet-specific CD4+ T-cell clone derived from the NOD mouse whose natural target antigen is unknown. A biometrical analysis of screening data from BDC2.5 T-cells and a positional scanning synthetic combinatorial library (PS-SCL) was used to analyze and rank all peptides in public viral and bacterial protein databases and identify potential molecular mimic sequences with predicted reactivity. Selected sequences were synthesized and tested for stimulatory activity with BDC2.5 T-cells. Active peptides were identified, and some of them were also able to stimulate spontaneously activated T-cells derived from young, pre-diabetic NOD mice, indicating that the reactivity of the BDC2.5 T-cell is directed at numerous mouse peptides. Our results provide evidence for their possible role as T-cell ligands involved in the activation of diabetogenic T-cells.
- APC, antigen-presenting cell
- hCMV; human cytomegalovirus
- MHC, major histocompatibility complex
- PS-SCL, positional scanning synthetic combinatorial library
- SI, stimulation index
- TCC, T-cell clone
- TCR, T-cell receptor
Footnotes
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V.A.J. and G.M.A. contributed equally to this work.
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- Accepted March 19, 2004.
- Received October 20, 2003.
- DIABETES
