Immunogenic Properties of an Anti-DNA Antibody- Derived Peptide, 88H.64-80: Location of a Dominant Idiotope Defined by T and B Cells

Abstract

Immunization of normal (BALB/c×NZW)F1H-2d×umice with peptide 88H.64-80 derived from the framework (FR) 3 VH region sequence of anti-DNA mAb, V-88, induces the production of IgG anti-peptide antibodies which cross-react specifically with the parent mAb. However, immunization of these normal mice with peptide 88H.64-80 sometimes provokes increased production of anti-dsDNA antibodies. A set of alanine substitute homologues of peptide 88H.64-80 were made to identify the amino acid residues that contribute to the antigenic status of the peptide. Peptide 88H.64-80 contained an antibody epitope at the carboxyl terminus of the peptide, while substitution of particular residues throughout the peptide had a significant inhibitory effect on T cell stimulation. Finally, subclass analysis of IgG anti-88H.64-80 peptide antibodies revealed a close correlation between the production of IgG2aanti-peptide antibodies (associated with a TH1 T cell response) and the production of IgG anti-dsDNA antibodies, but there was no correlation with any other antibody subclass. Despite the ability of peptide 88H.64-80 to provoke both the production of anti-dsDNA antibodies as well as anti-V region antibodies, the sequence of this peptide differs by only one amino acid residue from a number of murine germline gene-encoded homologues. Peptide 88H.64-80 probably represents an epitope whose appearance correlates with the level of expression of the VH genes that carry its sequence, and as such is characteristic of cross-reactive idiotypes associated with pathology.