Structural basis of stimulatory anti-idiotypic antibodies.

In order to design and produce effective vaccines based upon the idiotype network hypothesis of Jerne, a thorough understanding of the biological and structural aspects underlying the stimulating activities of anti-idiotypic antibodies is needed. Here we determined the nucleotide sequence of the variable heavy and light chain regions of two monoclonal anti-idiotypic antibodies which induce different anti-phosphorylcholine responses. The nucleotide sequences of the variable domains of two monoclonal anti-TEPC 15 (T15) antibodies (F6-3 and 4C11) were determined by the primer extension and Maxam-Gilbert techniques. The nucleotide sequence data show that 4C11 and F6-3 have homologous VH segments and JH segments, but different D regions. The VH segments of both clones belongs to the J558 VH family. Most of the differences among the VH segments are located in CDR2. The VK segments of 4C11 and F6-3 are homologous to the VK gene group 4 and group 8, respectively. Comparison of the sequences of 4C11 and F6-3 with other published anti-idiotype antibodies shows that there is no preferential utilization of immunoglobulin genes. An analysis of the distribution of charged residues and hydropathic comparison studies were used to interpret the sequence of 4C11 in terms of the biological mimicry of antigenic stimulation.