TCR V-BETA USAGE BY ACETYLCHOLINE RECEPTOR-SPECIFIC CD4(-CELLS IN MYASTHENIA-GRAVIS() T)

In myasthenia gravis the muscle acetylcholine receptor (AChR) is the t arget of an autoimmune response. AChR epitopes recognized by CD4(+) T cells in myasthenic patients have been identified. AChR-specific CD4() cell lines can be propagated by stimulation of blood lymphocytes wit h synthetic or biosynthetic AChR sequences. We analysed, using a semi- quantitative PCR assay, the T cell receptor (TCR) V beta usage of 16 a nti-AChR polyclonal CD4(+) T cell lines of known epitope specificity, propagated from myasthenic patients using pools of overlapping peptide s corresponding to the sequence of an AChR subunit, or individual synt hetic AChR sequences. Twelve lines had been propagated for less than 2 months, four lines for 3.5-5 months. Most lines had Limited V beta us age, but in most cases different V beta regions were used for differen t epitopes in the same patient, and for the same epitope in different patients. In a few patients, the same V beta regions were used for rec ognition of different epitopes. The V beta 4 and V beta 6 regions were used most frequently. These findings suggest that the potentially aut oimmune T cells that survive clonal deletion have a limited TCR repert oire. Although the present data do allow conclusions on the role of a superantigen in triggering the anti-AChR autoimmune response, the find ing that different V beta regions were used in different patients does not support an important role of a superantigen in the maintenance of the CD4(+) response in myasthenia gravis. (C) 1997 Academic Press Lim ited.