Preferential pairing of T and B cells for production of antibodies without covalent association of T and B epitopes

T cell from H-2b mice recognize at least 12 sequence regions on the Torpedo acetylcholine receptor (TAChR) α, γ and δ subunits. Immunization of C57BL/6 mice with individual synthetic TAChR sequences known to contain CD4+ epitopes resulted in most cases (10 out of 12 peptides) in anti-peptide antibody (Ab) production, indicating that short TAChR sequences contain both CD4+ and B epitopes. Immunization of C57BL/6 mice with a mixture of a CD4+ epitope peptide, from the TAChR or from an unrelated protein, plus another TAChR sequence forming a “pure” B epitope (Tα63–80), induced in most cases anti-peptide Ab and CD4+ cell sensitization only against the peptide containing the CD4+ epitope. However, when the T epitope peptide Tα360–378 was co-injected with the B epitope, Ab were also produced against the B epitope peptide. Injection of the individual peptides Tα360–378 and Tα63–80 at different and distant sites along the back of mice elicited sensitization of CD4+ cells and Ab production only against peptide Tα360–378. Therefore, when optimal cooperation between T and B cells occurs, spatial proximity but not covalent association of the B and the CD4+ epitope is necessary for production of Ab against the B epitope.