Synthetic peptides fail to induce nasal tolerance to experimental autoimmune myasthenia gravis.
Nasal administration of Torpedo acetylcholine receptor (AChR) to Lewis rats prior to induction of experimental autoimmune myasthenia gravis (EAMG) is highly efficient in prevention of clinical weakness, and suppression of AChR-specific T and B cell responses. To identify possible antigenic determinants within the receptor which can modulate EAMG and anti-AChR response, we evaluated the effects of nasal administration of alpha 61-76, alpha 100-116, alpha 146-162, delta 354-367, and alpha 261-277 of Torpedo AChR at different doses on the tolerance induction against EAMG irrespective if given at lower, the same or higher doses than whole Torpedo AChR protein, that was confirmed to be highly efficient as tolerogen to EAMG. None of these peptides, neither administrated alone nor in combination, induced tolerance to EAMG. Peptide administration did not affect the levels or affinities of anti-AChR antibodies when compared with non-tolerized control EAMG rats, while administration of whole AChR protein affected both variables. The results may indicate that the T and B cell heterogeneity of AChR epitopes makes it difficult to induce tolerance using synthetic peptide.
Zhang
G X
GX
Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Shi
F D
FD
Zhu
J
J
Xiao
B G
BG
Levi
M
M
Wahren
B
B
Yu
L Y
LY
Link
H
H
D000818:Animals; D000906:Antibodies / Q000032:analysis; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D009132:Muscles / Q000503:physiopathology; D009157:Myasthenia Gravis / Q000276:immunology* / Q000503:physiopathology; D009296:Nasal Cavity / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D011950:Receptors, Cholinergic / Q000737:chemistry / Q000276:immunology*; D014101:Torpedo
D000906:Antibodies; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011950:Receptors, Cholinergic