title: Human anti-idiotypic T cells induced by TCR peptides corresponding to a common CDR3 sequence motif in myelin basic protein-reactive T cells.
abstract: T cells recognizing myelin basic protein (MBP) are potentially involved in the pathogenesis of multiple sclerosis (MS). In vivo clonal expansion of MBP-reactive T cells in MS may relate in part to dysfunction of peripheral regulatory mechanisms, including the anti-idiotypic immune network. In this study, we examined anti-idiotypic immune responses and the functional properties of anti-idiotypic T cells in patients with MS and healthy controls using TCR peptides corresponding to a CDR3 sequence motif preferentially expressed among T cells recognizing the 83-99 immunodominant peptide of MBP in some patients with MS. The study demonstrated that anti-idiotypic T cells could be induced in vitro by 8mer and 15mer peptides containing the CDR3 motif in MS patients and healthy controls respectively. The estimated precursor frequency of the anti-idiotypic T cells was slightly reduced in MS patients compared to control subjects. The obtained anti-idiotypic T cells recognizing the 15mer TCR peptide were found to express the CD4 phenotype, produce predominantly IL-10 and inhibit the proliferation of autologous T cells recognizing the immunodominant peptide of MBP. Anti-idiotypic T cells induced by the 8mer TCR peptide were predominantly CD8+ cytotoxic T cells and exhibited cytotoxic activity against autologous MBP-specific T cells expressing the CDR3 sequence. When added in primary culture, both TCR peptides had a significant inhibitory effect on the T cell responses to the immunodominant peptide of MBP. The findings suggest that anti-idiotypic immune responses can be activated by selected TCR peptides and may play an important role in the in vivo regulation of MBP-reactive T cells.
authors.affiliation: Multiple Sclerosis Research Unit, Department of Neurology and Baylor-Methodist Multiple Sclerosis Center, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Ying C Q
authors.initials: YC
authors.lastname: Zang
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
authors.forename: Victor M
authors.initials: VM
authors.lastname: Rivera
authors.forename: James
authors.initials: J
authors.lastname: Killian
authors.forename: Jingwu Z
authors.initials: JZ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000888:Antibodies, Anti-Idiotypic; D022801:Complementarity Determining Regions; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; C104448:myelin basic protein 83-99