Single amino acid analogs of a myasthenogenic peptide modulate specific T cell responses and prevent the induction of experimental autoimmune myasthenia gravis.
Peptide p259-271 of the human acetylcholine receptor alpha-subunit, preferentially stimulates T cells of patients with myasthenia gravis (MG) and is an immunodominant epitope for T cells of BALB/c mice. A p259-271 specific T cell line of BALB/c origin was established and was shown to induce experimental MG in naive mice. Seven analogs of p259-271 were synthesized, and two of them were found to inhibit the p259-271 specific proliferative responses of the line and of p259-271 primed lymph node cells. Moreover, the most efficient inhibitor, analog 262Lys, prevented the MG related manifestations in mice inoculated with the line, and might be of potential value for the treatment of MG.
Katz-Levy
Y
Y
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Dayan
M
M
Wirguin
I
I
Fridkin
M
M
Sela
M
M
Mozes
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000378:metabolism; D001327:Autoimmune Diseases / Q000517:prevention & control*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000209:etiology* / Q000517:prevention & control*; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000235:genetics*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D016207:Cytokines; D010446:Peptide Fragments; D011950:Receptors, Cholinergic