International Immunology, Vol. 14, No. 12, pp. 1439-1447,
December 2002
© 2002 Japanese Society for Immunology
FEATURED ARTICLE OF THE MONTH |
Evidence for shared recognition of a peptide ligand by a diverse panel of non-obese diabetic mice-derived, islet-specific, diabetogenic T cell clones
1 Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University,3-1 Yamada-oka, Suita 565-0871, Japan 2 Barbara Davis Center for Childhood Diabetes and Department of Immunology, University of Colorado Health Sciences Center, Denver, CO 80262, USA 3 Division of Molecular Population Genetics, Department of Molecular Genetics and 4 Division of Immunogenetics, Department of Immunology and Neuroscience, Medical Institute of Bioregulation, and 5 Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Corp., Kyushu University, Fukuoka 812-8582, Japan 6 Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany 7 Research Institute for Biological Sciences, Science University of Tokyo, Noda 278-8510, Japan 8 International Medical Center of Japan, Tokyo 162-8655, Japan 9 Present address: Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA 10 Present address: National Minami Fukuoka Chest Hospital, Fukuoka 811-1394, Japan
Correspondence to: H. Kikutani; E-mail: kikutani{at}ragtime.biken.osaka-u.ac.jp
Transmitting editor: K. Inaba
MHC class II-restricted autoreactive T cells play a major role in the development of autoimmune diabetes mellitus in both human and mouse. Two of our groups previously established panels of islet-reactive CD4+ T cell clones from prediabetic non-obese diabetic (NOD) mice. These clones express distinct sets of TCR V
, Vß, J and Jß, and also differ in the structure of the junctional region of TCR. All of the T cell clones have been shown to cause insulitis and several induce diabetes when transferred to various recipients. The antigen specificities of these T cell clones have not been determined, but they do not react with defined islet cell antigens such as glutamic acid decarboxylase. To identify the peptide ligands recognized by these clones, we examined the reactivity of the T cell clones to peptide mixtures in which anchor residues for H2-Ag7 were fixed. Most of the clones showed similar reactivity to the peptide mixtures. To further determine the peptide ligands of the T cell clones, we synthesized several peptides based on the favored amino acid motifs and examined clone reactivity to the synthetic peptides. Some of the peptides, e.g. HLAI-RM and HIPI-RM, could stimulate most of the T cell clones tested, even though the clones expressed different TCR. The results suggest that our islet-reactive T cell clones recognize in islet ß cells a natural ligand that is similar to these peptides.
Keywords: autoantigens, combinatorial peptide libraries, islet-reactive T cells, MHC class II I-Ag7, peptide epitope
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