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
Mhm. Wauben et al., 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, European Journal of Immunology, 26(12), 1996, pp. 2866-2875
To assess the capacity of major histocompatibility complex (MHC) class
II- binding competitor peptides in inhibiting antibody-mediated disea
se 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 rec
eptors, was induced by immunization with Torpedo californica acetylcho
line receptor emulsified in complete Freund's adjuvant. The immunodomi
nant acetylcholine receptor T cell epitope was recognized by T cells i
n 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 recept
or. Co-immunization of peptide OVA323-339, a strong RT1.B-L-binding co
mpetitor peptide, resulted in complete disease inhibition. Although, t
he priming of the anti-acetylcholine receptor T cell response was not
fully inhibited, the kinetics of the response was changed. Moreover, b
esides a drastic reduction of the anti-Torpedo acetylcholine receptor
antibody titers, a shift in isotype distribution was found. These find
ings indicate that antibody-mediated autoimmune processes can be suppr
essed by MHC class II competitor peptides. Furthermore, the administra
tion of such peptides in vivo not only passively inhibits T cell activ
ation, but also functionary alters the immune response.