Anti-cyclosporine monoclonal antibodies and their anti-idiotopic counterpart: structure and biological activity. 1992

G Zenke, and G Zeder, and U Strittmatter, and E Andersen, and H P Kocher, and V F Quesniaux, and M H Schreier, and M H Van Regenmortel
Preclinical Research, Sandoz Pharma Ltd, Basel, Switzerland.

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.

UI MeSH Term Description Entries
D007108 Immune Tolerance The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. Immunosuppression (Physiology),Immunosuppressions (Physiology),Tolerance, Immune
D007135 Immunoglobulin Variable Region That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions. Variable Region, Ig,Variable Region, Immunoglobulin,Framework Region, Immunoglobulin,Fv Antibody Fragments,Fv Fragments,Ig Framework Region,Ig Variable Region,Immunoglobulin Framework Region,Immunoglobulin Fv Fragments,Immunoglobulin V,Antibody Fragment, Fv,Antibody Fragments, Fv,Fragment, Fv,Fragment, Fv Antibody,Fragment, Immunoglobulin Fv,Fragments, Fv,Fragments, Fv Antibody,Fragments, Immunoglobulin Fv,Framework Region, Ig,Framework Regions, Ig,Framework Regions, Immunoglobulin,Fv Antibody Fragment,Fv Fragment,Fv Fragment, Immunoglobulin,Fv Fragments, Immunoglobulin,Ig Framework Regions,Ig Variable Regions,Immunoglobulin Framework Regions,Immunoglobulin Fv Fragment,Immunoglobulin Variable Regions,Regions, Immunoglobulin Variable,Variable Regions, Ig,Variable Regions, Immunoglobulin
D007143 Immunoglobulin Heavy Chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa. Immunoglobulins, Heavy-Chain,Heavy-Chain Immunoglobulins,Ig Heavy Chains,Immunoglobulin Heavy Chain,Immunoglobulin Heavy Chain Subgroup VH-I,Immunoglobulin Heavy Chain Subgroup VH-III,Heavy Chain Immunoglobulins,Heavy Chain, Immunoglobulin,Heavy Chains, Ig,Heavy Chains, Immunoglobulin,Immunoglobulin Heavy Chain Subgroup VH I,Immunoglobulin Heavy Chain Subgroup VH III,Immunoglobulins, Heavy Chain
D007147 Immunoglobulin Light Chains Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kDa. There are two major types of light chains, kappa and lambda. Two Ig light chains and two Ig heavy chains (IMMUNOGLOBULIN HEAVY CHAINS) make one immunoglobulin molecule. Ig Light Chains,Immunoglobulins, Light-Chain,Immunoglobulin Light Chain,Immunoglobulin Light-Chain,Light-Chain Immunoglobulins,Chains, Ig Light,Chains, Immunoglobulin Light,Immunoglobulins, Light Chain,Light Chain Immunoglobulins,Light Chain, Immunoglobulin,Light Chains, Ig,Light Chains, Immunoglobulin,Light-Chain, Immunoglobulin
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D003429 Cross Reactions Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen. Cross Reaction,Reaction, Cross,Reactions, Cross
D004306 Dose-Response Relationship, Immunologic A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell. Immunologic Dose-Response Relationship,Relationship, Immunologic Dose-Response,Dose Response Relationship, Immunologic,Dose-Response Relationships, Immunologic,Immunologic Dose Response Relationship,Immunologic Dose-Response Relationships,Relationship, Immunologic Dose Response,Relationships, Immunologic Dose-Response
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked

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