Preferential recognition of TCR hypervariable regions by human anti-idiotypic T cells induced by T cell vaccination.
T cell responses to myelin basic protein (MBP) are potentially involved in the pathogenesis of multiple sclerosis (MS). Immunization with irradiated MBP-reactive T cells (T cell vaccination) induces anti-idiotypic T cell responses that suppress circulating MBP-reactive T cells. This T cell-T cell interaction is thought to involve the recognition of TCR expressed on target T cells. The study was undertaken to define the idiotypic determinants responsible for triggering CD8+ cytotoxic anti-idiotypic T cell responses by T cell vaccination in patients with MS. A panel of 9-mer synthetic TCR peptides corresponding to complementarity-determining region 2 (CDR2) and CDR3 of the immunizing MBP-reactive T cell clones were used to isolate anti-idiotypic T cell lines from immunized MS patients. The resulting TCR-specific T cell lines expressed exclusively the CD8 phenotype and recognized preferentially the CDR3 peptides. CDR3-specific T cell lines were found to lyze specifically autologous immunizing MBP-reactive T cell clones. The findings suggest that CDR3-specific T cells represented anti-idiotypic T cell population induced by T cell vaccination. In contrast, the CDR2 peptides were less immunogenic and contained cryptic determinants as the CDR2-specific T cell lines did not recognize autologous immunizing T cell clones from which the peptide sequence was derived. The study has important implications in our understanding of in vivo idiotypic regulation of autoimmune T cells and the regulatory mechanism underlying T cell vaccination.
Zang
Y C
YC
Multiple Sclerosis Research Laboratory, Department of Neurology and Baylor-Methodist Multiple Sclerosis Center, Baylor College of Medicine, Houston, TX 77030, USA.
Hong
J
J
Rivera
V M
VM
Killian
J
J
Zhang
J Z
JZ
D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D002460:Cell Line; D002469:Cell Separation; D002999:Clone Cells / Q000276:immunology / Q000637:transplantation; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000378:metabolism; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation / Q000276:immunology; D017710:Lymphocyte Transfusion; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism*; D014611:Vaccination / Q000379:methods
D000888:Antibodies, Anti-Idiotypic; D007130:Immunoglobulin Idiotypes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta