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

• Published in: Journal of autoimmunity 1998-10, Vol.11 (5), p.439-447
• Main Authors: Ward, F.J., Khan, N., Wolger, L.J., Howe, C.A., Eivazova, E.R., Harper, N., Muller, S., Staines, N.A.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; anti-DNA antibody; Antibodies, Antinuclear - chemistry; Antibodies, Antinuclear - genetics; Antibodies, Antinuclear - immunology; Antibodies, Monoclonal - chemistry; Antibodies, Monoclonal - genetics; Antibodies, Monoclonal - immunology; B-Lymphocytes - immunology; Cross Reactions; DNA - chemistry; DNA - immunology; Humans; Immunization; Immunodominant Epitopes - chemistry; Immunodominant Epitopes - genetics; Immunoglobulin G - biosynthesis; Immunoglobulin Heavy Chains - chemistry; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Idiotypes - chemistry; Immunoglobulin Idiotypes - genetics; Immunoglobulin Idiotypes - immunology; In Vitro Techniques; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Peptide Fragments - chemistry; Peptide Fragments - genetics; Peptide Fragments - immunology; systemic lupus erythematosus; T cell; T-Lymphocytes - immunology
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1006/jaut.1998.0234

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.