glutamic acid decarboxylase-derived epitopes with specific domains expand cd4+cd25+ regulatory t cells谷氨酸decarboxylase-derived抗原表位与特定的领域扩大cd4 + cd25 +调节性t细胞.pdfVIP

Glutamic Acid Decarboxylase-Derived Epitopes with Specific Domains Expand CD4+CD25+ Regulatory T Cells 1. 1. 1. 1 1 1 Guojiang Chen , Gencheng Han , Jiannan Feng , Jianan Wang , Renxi Wang , Ruonan Xu , Beifen 1 2 1 Shen , Jiahua Qian , Yan Li * 1 Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, P.R. China, 2 National Cancer Institute, Vaccine branch, Bethesda, Maryland, United States of America Abstract + + Background: CD4 CD25 regulatory T cell (Treg)-based immunotherapy is considered a promising regimen for controlling the progression of autoimmune diabetes. In this study, we tested the hypothesis that the therapeutic effects of Tregs in response to the antigenic epitope stimulation depend on the structural properties of the epitopes used. Methodology/Principal Findings: Splenic lymphocytes from nonobese diabetic (NOD) mice were stimulated with different glutamic acid decarboxylase (GAD)-derived epitopes for 7–10 days and the frequency and function of Tregs was analyzed. We found that, although all expanded Tregs showed suppressive functions in vitro, only p524 (GAD524–538)-expanded CD4+CD25+ T cells inhibited diabetes development in the co-transfer models, while p509 (GAD509–528)- or p530 (GAD530– 543)-expanded CD4+CD25+ T cells had no such effects. Using computer-guided molecular modeling and docking methods, the differences in structural characteristics of these epitopes and the interaction mode (including binding energy and identified domains in the epitopes) between the above-mentioned e