CD4(+) T cell repertoire on the epsilon subunit of muscle acetylcholine receptor in myasthenia gravis

We have identified sequence regions of the human muscle acetylcholine recep tor epsilon subunit recognized by CD4(+) T cells from myasthenia gravis pat ients. We tested the proliferative response in vitro of blood CD4(+) cells from 18 myasthenic patients and 5 controls, to individual overlapping synth etic peptides spanning the epsilon subunit sequence. All patients recognize d a complex epitope repertoire. The peptides recognized by the CD4(+) cells included sequence regions of the epsilon subunit that were diverged as com pared to the homologous sequences of the other receptor subunits. Recogniti on of epitopes formed by sequence regions unique to the epsilon subunit sug gests a direct role of this subunit in sensitizing the CD4(+) cells. Severa l epsilon subunit peptides were recognized by many patients. Thus the epsil on subunit, like other acetylcholine receptor subunits, forms 'universal' C D4(+) epitopes. The healthy subjects recognized some epsilon subunit peptid es sporadically and at a low level. (C) 1998 Elsevier Science B.V. All righ ts reserved.