Restricted T cell receptor repertoire for acetylcholine receptor in murine myasthenia gravis

Immunization of C57BL/6 mice with AChR provokes symptoms similar to those seen in the disease myasthenia gravis. To elucidate the structural requirements for T cell recognition of AChR and to identify TcR features which might provide targets for immunotherapy, a panel of T cell hybridomas was generated after immunization of mice with the immunodominant peptide of the AChR α chain. The TcR genes expressed by these hybridomas were sequenced. TcR-Vβ6 was preferentially employed, but other Vβ genes were also observed. A conserved acidic residue was present in all CDR3 regions, regardless of the Vβ. The TcR-Vα repertoire was somewhat skewed with three Vα families accounting for 82% of the sequences. The utilization of multiple T cell receptor Vβ genes may contribute to the inability to inhibit EAMG by elimination of Vβ6 + T cells.