TCR V beta usage by acetylcholine receptor-specific CD4+ T cells in myasthenia gravis.
In myasthenia gravis the muscle acetylcholine receptor (AChR) is the target 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 with synthetic or biosynthetic AChR sequences. We analysed, using a semi-quantitative PCR assay, the T cell receptor (TCR) V beta usage of 16 anti-AChR polyclonal CD4+ T cell lines of known epitope specificity, propagated from myasthenic patients using pools of overlapping peptides corresponding to the sequence of an AChR subunit, or individual synthetic 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 usage, but in most cases different V beta regions were used for different 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 recognition of different epitopes. The V beta 4 and V beta 6 regions were used most frequently. These findings suggest that the potentially autoimmune T cells that survive clonal deletion have a limited TCR repertoire. Although the present data do allow conclusions on the role of a superantigen in triggering the anti-AChR autoimmune response, the finding 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.
Raju
R
R
Department of Biochemistry, College of Biological Sciences, University of Minnesota, St Paul 55018, USA.
Navaneetham
D
D
Protti
M P
MP
Horton
R M
RM
Hoppe
B L
BL
Howard
J
J
Conti-Fine
B M
BM
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D017931:DNA Primers; D000939:Epitopes / Q000032:analysis / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D009157:Myasthenia Gravis / Q000276:immunology* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000235:genetics; D011950:Receptors, Cholinergic / Q000032:analysis* / Q000235:genetics
D017931:DNA Primers; D000939:Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011950:Receptors, Cholinergic