title: Evidence for shared recognition of a peptide ligand by a diverse panel of non-obese diabetic mice-derived, islet-specific, diabetogenic T cell clones.
abstract: 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 alpha , V beta , J alpha and J beta , 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-A g7 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 beta cells a natural ligand that is similar to these peptides.
authors.affiliation: Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University,3-1 Yamada-oka, Suita 565-0871, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yoshida
authors.forename: Tracy
authors.initials: T
authors.lastname: Martin
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Cathleen
authors.initials: C
authors.lastname: Dobbs
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kamikawaji
authors.forename: Naoko
authors.initials: N
authors.lastname: Nakano
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Takehiko
authors.initials: T
authors.lastname: Sasazuki
authors.forename: Kathryn
authors.initials: K
authors.lastname: Haskins
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikutani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002999:Clone Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D008024:Ligands; D051379:Mice; D016688:Mice, Inbred NOD; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D008024:Ligands; D019151:Peptide Library; D010455:Peptides