Clustering of B and T Epitopes Within Short Sequence Regions of the Nieotinic 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 a 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 TAChRα, β and δ 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.