Discovery of low-affinity preproinsulin epitopes and detection of autoreactive CD8 T-cells using combinatorial MHC multimers
作者: Wendy W. UngerJurjen VelthuisJoana R.F. AbreuSandra LabanEdwin QuintenMichel G.D. KesterSine Reker-HadrupArnold H. BakkerGaby DuinkerkenArend MulderKees L.M.C. FrankenRobert HilbrandsBart KeymeulenMark PeakmanFerry OssendorpJan Wouter DrijfhoutTon N. SchumacherBart O. Roep
作者单位: 1Department of Immunohematology & Blood Transfusion, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
2Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
3Division of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
4Diabetes Research Center, Free University Brussels – VUB, Brussels, Belgium
5Department of Immunobiology, King’s College London School of Medicine, Guy’s Hospital, London SE1 9RT, UK
6National Institute of Health Research Biomedical Research Centre at Guy’s & St Thomas’ NHS Foundation Trust and King’s College London, London SE1 9RT, UK
刊名: Journal of Autoimmunity, 2011, Vol.37 (3), pp.151-159
来源数据库: Elsevier Journal
DOI: 10.1016/j.jaut.2011.05.012
关键词: PreproinsulinCD8 T-cellType 1 diabetesAutoreactiveImmunotherapy
英文摘要: Abstract(#br)Autoreactive cytotoxic CD8 T-cells (CTLs) play a key pathogenic role in the destruction of insulin-producing beta-cells resulting in type 1 diabetes. However, knowledge regarding their targets is limited, restricting the ability to monitor the course of the disease and immune interventions. In a multi-step discovery process to identify novel CTL epitopes in human preproinsulin (PPI), PPI was digested with purified human proteasomes, and resulting COOH-fragments aligned with algorithm-predicted HLA-binding peptides to yield nine potential HLA-A1, -A2, -A3 or -B7-restricted candidates. An UV-exchange method allowed the generation of a repertoire of multimers including low-affinity HLA-binding peptides. These were labeled with quantum dot-fluorochromes and encoded in a...
全文获取路径: Elsevier  (合作)
影响因子:8.145 (2012)