Reactivity and regulatory properties of human anti-idiotypic antibodies induced by T cell vaccination.
Immunization with irradiated autoreactive T cells (T cell vaccination) induces anti-idiotypic T cell responses that preferentially recognize complementarity-determining region 3 sequences, contributing to clonal depletion of autoreactive T cells. However, it remains unknown whether T cell vaccination elicits anti-idiotypic humoral responses and whether the anti-idiotypic Abs play a similar role in the regulatory mechanism induced by T cell vaccination. In this study we examined the occurrence, the reactivity pattern, and the regulatory role of anti-idiotypic Abs elicited by T cell vaccination in patients with multiple sclerosis. We demonstrated for the first time that B cells producing anti-idiotypic Abs could be isolated from vaccinated patients. These EBV-transformed B cell lines were selected for specific reactivity to a 20-mer TCR peptide incorporating a common complementarity-determining region 3 sequence of the immunizing T cell clones. The resulting anti-idiotypic Abs were found to react with the original immunizing T cell clones and exhibit an inhibitory effect on their proliferation. The findings suggest that anti-idiotypic Ab responses can be induced by T cell vaccination in humans and that their regulatory properties are likely to contribute to the suppression of myelin basic protein-reactive T cells in vaccinated patients. The study has important implications in our understanding of the regulatory role of the anti-idiotypic humoral responses induced by T cell vaccination.
Hong
J
J
Multiple Sclerosis Research Laboratory, Department of Neurology, and Baylor-Methodist Multiple Sclerosis Center, Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Zang
Y C
YC
Tejada-Simon
M V
MV
Li
S
S
Rivera
V M
VM
Killian
J
J
Zhang
J Z
JZ
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology*; D000917:Antibody Formation; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001666:Binding Sites, Antibody; D002461:Cell Line, Transformed; D002999:Clone Cells / Q000737:chemistry / Q000276:immunology / Q000637:transplantation; D006801:Humans; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology / Q000628:therapy; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000637:transplantation*; D014611:Vaccination / Q000379:methods
D000888:Antibodies, Anti-Idiotypic; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C104448:myelin basic protein 83-99