Abstract
Thymulin is a nonapeptide hormone produced by thymic epithelial cells. Its biological activity is strictly dependent on the presence of the metal zinc in the molecule. Antithymulin monoclonal antibodies have been produced against either the synthetic (AS1) or the natural intraepithelial (AE1) molecule. These monoclonal antibodies were screened for their abilities to inhibit the zinc-dependent biological activity of the hormone and were shown to bind to thymic epithelial cells. By using biological and immunofluorescence assays, the two antibodies were shown to recognize exclusively the zinc-coupled thymulin molecule. Other antithymulin antibodies screened by RIA or ELISA (using a zinc-deprived substrate) recognized a zinc-independent epitope on the thymulin molecule. These data indicate the existence of a zinc-specific conformation on the thymulin molecule. They are in agreement with NMR studies showing that the zinc-containing hormone has a unique structure.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arquilla E. R., Thiene P., Brugman T., Ruess W., Sugiyama R. Effects of zinc ion on the conformation of antigenic determinants on insulin. Biochem J. 1978 Oct 1;175(1):289–297. doi: 10.1042/bj1750289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bensman A., Dardenne M., Murnaghan K., Vasmant D., Bach J. F. Decreased biological activity of serum thymic hormone (thymulin) in children with nephrotic syndrome. Int J Pediatr Nephrol. 1984 Dec;5(4):201–204. [PubMed] [Google Scholar]
- Berrih S., Savino W., Azoulay M., Dardenne M., Bach J. F. Production of anti-thymulin (FTS) monoclonal antibodies by immunization against human thymic epithelial cells. J Histochem Cytochem. 1984 Apr;32(4):432–438. doi: 10.1177/32.4.6200531. [DOI] [PubMed] [Google Scholar]
- Dardenne M., Pléau J. M., Nabarra B., Lefrancier P., Derrien M., Choay J., Bach J. F. Contribution of zinc and other metals to the biological activity of the serum thymic factor. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5370–5373. doi: 10.1073/pnas.79.17.5370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dardenne M., Savino W., Wade S., Kaiserlian D., Lemonnier D., Bach J. F. In vivo and in vitro studies of thymulin in marginally zinc-deficient mice. Eur J Immunol. 1984 May;14(5):454–458. doi: 10.1002/eji.1830140513. [DOI] [PubMed] [Google Scholar]
- Furie B., Furie B. C. Conformation-specific antibodies as probes of the gamma-carboxyglutamic acid-rich region of bovine prothrombin. Studies of metal-induced structural changes. J Biol Chem. 1979 Oct 10;254(19):9766–9771. [PubMed] [Google Scholar]
- Gastinel L. N., Dardenne M., Pleau J. M., Bach J. F. Studies on the zinc binding site to the serum thymic factor. Biochim Biophys Acta. 1984 Feb 14;797(2):147–155. doi: 10.1016/0304-4165(84)90116-8. [DOI] [PubMed] [Google Scholar]
- Jambon B., Montagne P., Bene M. C., Brayer M. P., Faure G., Duheille J. Immunohistologic localization of "facteur thymique serique" (FTS) in human thymic epithelium. J Immunol. 1981 Nov;127(5):2055–2059. [PubMed] [Google Scholar]
- Monier J. C., Dardenne M., Pléau J. M., Schmitt D., Deschaux P., Bach J. F. Characterization of facteur thymique sérique (FTS) in the thymus. I. Fixation of anti-FTS antibodies on thymic reticulo-epithelial cells. Clin Exp Immunol. 1980 Dec;42(3):470–476. [PMC free article] [PubMed] [Google Scholar]
- Ohga K., Incefy G. S., Wang C. Y., Good R. A. Generation of a monoclonal antibody against facteur thymique serique (FTS). Clin Exp Immunol. 1982 Mar;47(3):725–734. [PMC free article] [PubMed] [Google Scholar]
- Papiernik M., Nabarra B., Bach J. F. In vitro culture of functional human thymic epithelium. Clin Exp Immunol. 1975 Feb;19(2):281–287. [PMC free article] [PubMed] [Google Scholar]
- Pleau J. M., Dardenne M., Blouquit Y., Bach J. F. Structural study of circulating thymic factor: a peptide isolated from pig serum. II. Amino acid sequence. J Biol Chem. 1977 Nov 25;252(22):8045–8047. [PubMed] [Google Scholar]
- Savino W., Dardenne M., Papiernik M., Bach J. F. Thymic hormone-containing cells. Characterization and localization of serum thymic factor in young mouse thymus studied by monoclonal antibodies. J Exp Med. 1982 Aug 1;156(2):628–633. doi: 10.1084/jem.156.2.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Savino W., Huang P. C., Corrigan A., Berrih S., Dardenne M. Thymic hormone-containing cells. V. Immunohistological detection of metallothionein within the cells bearing thymulin (a zinc-containing hormone) in human and mouse thymuses. J Histochem Cytochem. 1984 Sep;32(9):942–946. doi: 10.1177/32.9.6379040. [DOI] [PubMed] [Google Scholar]