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Detection and Characterization of T Cells Specific for BDC2.5 T Cell-Stimulating Peptides¹

Sylvaine You^*, Cyndi Chen^*, Wen-Hui Lee^*, Chun-Hua Wu^*, Valeria Judkowski, Clemencia Pinilla, Darcy B. Wilson and Chih-Pin Liu^2,*

^* Division of Immunology, Beckman Research Institute, City of Hope, Duarte, CA 91010; and Torrey Pines Institute for Molecular Studies, San Diego, CA 92121

Nonobese diabetic (NOD) mice expressing the BDC2.5 TCR transgene are useful for studying type 1 diabetes. Several peptides have been identified that are highly active in stimulating BDC2.5 T cells. Herein, we describe the use of I-Ag7 tetramers containing two such peptides, p79 and p17, to detect and characterize peptide-specific T cells. The tetramers could stain CD4⁺ T cells in the islets and spleens of BDC2.5 transgenic mice. The percentage of CD4⁺, tetramer⁺ T cells increased in older mice, and it was generally higher in the islets than in the spleens. Our results also showed that tetAg7/p79 could stain a small population of CD4⁺ T cells in both islets and spleens of NOD mice. The percentage of CD4⁺, tetramer⁺ T cells increased in cells that underwent further cell division after being activated by peptides. The avidity of TCRs on purified tetAg7/p79⁺ T cells for tetAg7/p79 was slightly lower than that of BDC2.5 T cells. Although tetAg7/p79⁺ T cells, like BDC2.5 T cells, secreted a large quantity of IFN-, they were biased toward being IL-10-producing cells. Additionally, <3% of these cells expressed TCR V4. In vivo adoptive transfer experiments showed that NOD/scid recipient mice cotransferred with tetAg7/p79⁺ T cells and NOD spleen cells, like mice transferred with NOD spleen cells only, developed diabetes. Therefore, we have generated Ag-specific tetramers that could detect a heterogeneous population of T cells, and a very small number of NOD mouse T cells may represent BDC2.5-like cells.

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