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 sequenc es 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. Immunizatio n of C57BL/6 mice with a mixture of a CD4(+) epitope peptide, from the TAChR or from an unrelated protein, plus another TAChR sequence formi ng a ''pure'' B epitope (T alpha 63-80), induced in most cases anti-pe ptide Ab and CD4(+) cell sensitization only against the peptide contai ning the CD4(+) epitope. However, when the T epitope peptide T alpha 3 60-378 was co-injected with the B epitope, Ab were also produced again st 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 ba ck of mice elicited sensitization of CD4(+) cells and Ab production on ly against peptide T alpha 360-378. Therefore, when optimal cooperatio n between T and B cells occurs, spatial proximity but not covalent ass ociation of the B and the CD4(+) epitope is necessary for production o f Ab against the B epitope.