Clustering of B and T epitopes within short sequence regions of the nicotinic acetylcholine receptor.
The epitope repertoire of B cells, due to their selective ability to process their specific antigen and the potential bias imposed on the resulting peptides by the surface immunoglobulins bound to the antigen, may influence the T-helper repertoire. Immunization of C57B1/6 mice with Torpedo acetylcholine receptor (TAChR) causes experimental autoimmune myasthenia gravis (EAMG). Anti-TAChR CD4+ cells recognize epitopes within three sequence regions of the TAChR alpha subunit ('dominant epitopes'). Immunization of mice with denatured or synthetic TAChR antigens sensitizes CD4+ cells to other TAChR sequence regions ('cryptic epitopes'). We investigated here whether clustering of B and T epitopes within the same short sequence segments occurs during the anti-TAChR response, as previously described for the response to hexogenous antigens unrelated to homologous self proteins. Twelve 19-20 residue synthetic sequences of the TAChR alpha, gamma and delta subunits, containing dominant or cryptic CD4+ epitopes for C57B1/6 mice, were tested for ability to induce anti-peptide antibody production. C57B1/6 mice were immunized with the individual peptides. Ten peptides stimulated antibody production. Therefore > 80% of these short TAChR sequences also contain B epitopes. Therefore also in the anti-TAChR response leading to EAMG T and B cell epitopes frequently reside within the same short sequence segment.
Bellone
M
M
Department of Biochemistry, College of Biological Sciences, University of Minnesota, St Paul.
Karachunski
P I
PI
Ostlie
N
N
Lei
S
S
Conti-Fine
B M
BM
D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D000939:Epitopes / Q000032:analysis; D016056:Immunodominant Epitopes / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011978:Receptors, Nicotinic / Q000276:immunology*; D014101:Torpedo
D000939:Epitopes; D016056:Immunodominant Epitopes; D011978:Receptors, Nicotinic