Inhibition of experimental autoimmune myasthenia gravis by major histocompatibility complex class II competitor peptides results not only in a suppressed but also in an altered immune response.
To assess the capacity of major histocompatibility complex (MHC) class II-binding competitor peptides in inhibiting antibody-mediated disease processes, we studied experimental autoimmune myasthenia gravis in Lewis rats. Experimental autoimmune myasthenia gravis, a disease model mediated by T cell-dependent autoantibodies against acetylcholine receptors, was induced by immunization with Torpedo californica acetylcholine receptor emulsified in complete Freund's adjuvant. The immunodominant acetylcholine receptor T cell epitope was recognized by T cells in the context of MHC class II RT1.B(L). The disease inhibitory capacity of RT1.B(L)-binding peptides not related to the acetylcholine receptor was determined upon co-immunization with Torpedo acetylcholine receptor. Co-immunization of peptide OVA323-339, a strong RT1.B(L)-binding competitor peptide, resulted in complete disease inhibition. Although, the priming of the anti-acetylcholine receptor T cell response was not fully inhibited, the kinetics of the response was changed. Moreover, besides a drastic reduction of the anti-Torpedo acetylcholine receptor antibody titers, a shift in isotype distribution was found. These findings indicate that antibody-mediated autoimmune processes can be suppressed by MHC class II competitor peptides. Furthermore, the administration of such peptides in vivo not only passively inhibits T cell activation, but also functionally alters the immune response.
Wauben
M H
MH
Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands. M.Wauben@vetmic.dgk.ruu.nl
Hoedemaekers
A C
AC
Graus
Y M
YM
Wagenaar
J P
JP
van Eden
W
W
de Baets
M H
MH
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000187:drug effects; D001667:Binding, Competitive / Q000276:immunology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism* / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects*; D007132:Immunoglobulin Isotypes / Q000187:drug effects / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology* / Q000517:prevention & control*; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology*; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000276:immunology
D001323:Autoantibodies; D000949:Histocompatibility Antigens Class II; D007132:Immunoglobulin Isotypes; D010455:Peptides; D011950:Receptors, Cholinergic; D010047:Ovalbumin