Paratope- and framework-related cross-reactive idiotopes on anti-acetylcholine receptor antibodies.
Cross-reactive idiotopes are a possible target for therapeutical interventions in autoimmune diseases. To investigate their role in the pathogenesis of experimental autoimmune myasthenia gravis (EAMG) we analyzed the Id of rat anti-AChR mAb 6, 35, 61, 65 and a control myeloma protein IR27. Anti-Id 6, 35, 61, 65 bound in a direct binding assay with various affinity to all rat anti-AChR mAb that were tested. Anti-Id IR27 recognized none of the anti-AChR mAb. The specificity of these crossreactions was confirmed by inhibition studies with anti-AChR mAb and two control rat myeloma proteins (IR27 and IR241). In addition, the Id expression on mAb D6, a mouse anti-human AChR mAb was recognized by anti-Id 6, 35, and 65. Anti-Id, except anti-Id IR27, bound to affinity purified IgG from the sera of rats with EAMG, but not to preimmune Lewis IgG. These results suggest extensive sharing of idiotopes among anti-AChR mAb, which are also present in EAMG serum. Anti-AChR mAb against the main immunogenic region (6, 35, 65) from different rat strains, shared at least one paratope-related cross-reactive idiotopes. In the view of the fact that anti-main immunogenic region antibodies might form a predominant fraction of the polyclonal response against AChR, it is conceivable that an anti-Id recognizing these antibodies could have therapeutical applications as for example a selective immune absorbent or in immunotoxin therapy.
Verschuuren
J J
JJ
University of Limburg, Department of Immunology, Maastricht, The Netherlands.
Graus
Y M
YM
Tzartos
S J
SJ
van Breda Vriesman
P J
PJ
De Baets
M H
MH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis*; D003429:Cross Reactions; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000032:analysis* / Q000276:immunology; D051379:Mice; D009157:Myasthenia Gravis / Q000276:immunology; D011817:Rabbits; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology*; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D007106:Immune Sera; D007130:Immunoglobulin Idiotypes; D011950:Receptors, Cholinergic