Genetic differences of combining sites of insulin antibodies and importance of C-terminal portion of the A chain to biological and immunological activity of insulin
| Autor: | Jack Finn, Edward R. Arquilla, Henri Ooms |
|---|---|
| Rok vydání: | 1966 |
| Předmět: |
Electrophoresis
Chemical Phenomena Insulin Antibodies Endocrinology Diabetes and Metabolism medicine.medical_treatment Guinea Pigs Radioimmunoassay Adipose tissue Phenylalanine Biology Hemolysis Antigen-Antibody Reactions Immune system Iodine Isotopes Genetics Internal Medicine medicine Animals Insulin Inbreeding Serologic Tests Amino Acid Sequence Polyacrylamide gel electrophoresis Antiserum Binding Sites Biological activity Fluoresceins Rats Chemistry Adipose Tissue Biochemistry biology.protein Tyrosine Biological Assay Rabbits Antibody |
| Zdroj: | Diabetologia. 2:1-13 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/bf01106969 |
| Popis: | Using an insoluble insulin complex, it was possible to demonstrate that antibodies to insulin produced in individual animals are directed towards different portions of the insulin molecule. Furthermore, using the antisera from two different inbred strains of guinea pigs and their F1 and F2 offspring, evidence is presented for the genetic control of combining site configurations of antibodies to insulin produced in guinea pigs. The importance of different portions of the insulin molecule to biological and immunological activity was investigated. The attachment of125I to insulin (reportedly to the tyrosines at positions 14 and/or 19 of the A chain) seems to impair both the biological and immunological activity of insulin. The distribution of antibody-bound and free125I-insulin was found to be different from the distribution of non-labeled insulin. Relatively pure125I-insulin was separated from non-labeled insulin by acrylamide gel electrophoresis, and was found to have markedly reduced immunological reactivity in the immune hemolysis inhibition assay. It was concluded that antibodies to insulin exist which cannot react with iodinated insulin. Furthermore, when tested in the rat adipose tissue assay, purified125I-insulin preparations had little or no biological activity. Conversely, mono-substituted fluorescein-labeled insulin (purified on acrylamide gel electrophoresis) appears to retain full immunological and biological competence. Fluorescein is thought to attach to the N-terminal phenylalanine of the B chain and/or to the N-terminal glycine of the A chain. It is concluded that these two residues contribute little to the biological and immunological integrity of insulin. Studies of this nature aid in elucidating the surface configuration of insulin, and thereby may contribute to an understanding of its tertiary structure. |
| Databáze: | OpenAIRE |
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