Anti-cyclosporine monoclonal antibodies and their anti-idiotopic counterpart: structure and biological activity

• Published in: Molecular immunology Vol. 29; no. 3; p. 343
• Main Authors: Zenke, G, Zeder, G, Strittmatter, U, Andersen, E, Kocher, H P, Quesniaux, V F, Schreier, M H, Van Regenmortel, M H
• Format: Journal Article
• Language: English
• Published: England 01.03.1992
• Subjects: Amino Acid Sequence; Animals; Antibodies, Anti-Idiotypic - chemistry; Antibodies, Anti-Idiotypic - immunology; Antibodies, Monoclonal - immunology; Antibody Specificity; Base Sequence; Binding, Competitive; Cross Reactions; Cyclosporine - immunology; Dose-Response Relationship, Immunologic; Enzyme-Linked Immunosorbent Assay; Female; Immune Tolerance - drug effects; Immunoglobulin Heavy Chains - chemistry; Immunoglobulin Light Chains - chemistry; Immunoglobulin Variable Region - chemistry; In Vitro Techniques; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Sequence Data; RNA, Messenger - genetics; Spleen - immunology
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/0161-5890(92)90021-O

In order to study the structural and functional mimicry of an antigen by anti-idiotypic antibodies, we generated anti-idiotopic monoclonal antibodies (anti-Id mAbs) against a mAb (R45-45-11) with specificity for the immunosuppressive cyclic undecapeptide cyclosporine (Cs; Sandimmune). Three out of five anti-Id mAbs inhibited the binding of Cs to the anti-Cs mAb R45-45-11. All anti-Id mAbs cross-reacted only with one (anti-Cs mAb V45-271-10) out of 19 anti-Cs mAbs. The anti-Cs mAb V45-271-10 recognizes an epitope on the Cs molecule which is very similar to that recognized by R45-45-11. R45-45-11 and V45-271-10 differ only by one amino acid in the variable region. The anti-Id mAbs which recognize combining site-associated idiotopes (Ids) reverse the blocking effect of the anti-Cs mAb R45-45-11 on Cs immunosuppression in vitro. The sequences of the variable regions of heavy and light chain of one anti-Id mAb were determined. X-ray analysis of the corresponding Fab fragment, either alone or complexed with the Fab fragment of the Id, is currently in progress.