Recruitment of multiple V β genes in the TCR repertoire against a single pathogenic thyroglobulin epitope

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 A s ‐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.