PREFERENTIAL PAIRING OF T-CELLS AND B-CELLS FOR PRODUCTION OF ANTIBODIES WITHOUT COVALENT ASSOCIATION OF T-EPITOPES AND B-EPITOPES

T cell from H-2(b) mice recognize at least 12 sequence regions on the Torpedo acetylcholine receptor (TAChR) alpha, gamma and delta 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 (T alpha 63-80), 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 T alpha 360-378 was co-injected with the B epitope, Ab were also produced against the B epitope peptide. Injection of the individual peptides T alpha 360-378 and T alpha 63-80 at different and distant sites along the back of mice elicited sensitization of CD4(+) cells and Ab production only against peptide T alpha 360-378. 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.