title: Recruitment of multiple V beta genes in the TCR repertoire against a single pathogenic thyroglobulin epitope.
abstract: In autoimmune thyroid disease, the question whether thyroid-infiltrating, autoreactive T cells are derived from a polyclonal or oligoclonal subset has been the subject of considerable debate. In this report, we have examined the T-cell receptor (TCR) V beta profile of mouse clonal T cells responding to a single thyroiditogenic epitope, the As-restricted, 9mer mouse thyroglobulin (MTg) peptide (2496-04). In vitro recall assays based on lymph node cell (LNC) proliferation and cytokine release demonstrated that this peptide is a minimal T-cell epitope inducing a T-helper 1 (Th1) type of response in SJL hosts. A panel of cloned, interleukin-2 (IL-2)-secreting hybridomas was generated from this Th1 subset and their TCR-V beta gene utilization was assessed by reverse transcription-polymerase chain reaction (RT-PCR). Ten clones derived from two independent fusions were found to utilize three V beta gene families (V beta 2, 4, and 17). To the extent that Tg or other thyroid autoantigens encompass multiple pathogenic epitopes it appears unlikely from these data that a restricted TCR-V beta chain usage will be a general characteristic of thyroiditogenic T cells.
authors.affiliation: Division of Endocrinology, Faculty of Medicine, Memorial University of Newfoundland, St John's, Canada.
authors.forename: V P
authors.initials: VP
authors.lastname: Rao
authors.forename: R S
authors.initials: RS
authors.lastname: Russell
authors.forename: G
authors.initials: G
authors.lastname: Carayanniotis
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006825:Hybridomas / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000276:immunology; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology*
chemical_list: D001324:Autoantigens; D016207:Cytokines; D000939:Epitopes; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013954:Thyroglobulin