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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1992 Jun 15;89(12):5507–5511. doi: 10.1073/pnas.89.12.5507

Zinc regulates the function of two superantigens.

J D Fraser 1, R G Urban 1, J L Strominger 1, H Robinson 1
PMCID: PMC49321  PMID: 1608962

Abstract

Staphylococcal enterotoxins bind with high affinity to class II major histocompatibility complex proteins and subsequently stimulate large numbers of T cells via the V beta portion of the T-cell receptor. Binding of enterotoxin A and enterotoxin E to HLA-DR was completely abolished by low levels of EDTA, whereas binding of toxic shock toxin was unaffected. Addition of Zn2+ to as little as 2 microM excess over EDTA completely reconstituted binding, but Ca2+, Mg2+, Cu2+, Fe2+, and Mn2+ had no effect. The dissociation constant (Kd) of 65Zn2+ binding to a single site on purified enterotoxin A was 2 microM, and addition of purified HLA-DR1 did not alter the Kd, indicating that the binding site was exclusive to enterotoxin A. In the presence of saturating levels of zinc the Kd for enterotoxin A binding to purified HLA-DR1 was 25 nM. Thus, zinc binding is an essential first step in the formation of the major histocompatibility complex binding domain of at least two bacterial superantigens. Given the measured Kd of zinc binding to enterotoxin A, serum levels of free zinc (0.2-1.0 microM) may well regulate the toxic sequelae by these two superantigens.

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Selected References

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  1. Acha-Orbea H., Shakhov A. N., Scarpellino L., Kolb E., Müller V., Vessaz-Shaw A., Fuchs R., Blöchlinger K., Rollini P., Billotte J. Clonal deletion of V beta 14-bearing T cells in mice transgenic for mammary tumour virus. Nature. 1991 Mar 21;350(6315):207–211. doi: 10.1038/350207a0. [DOI] [PubMed] [Google Scholar]
  2. Atkin C. L., Cole B. C., Sullivan G. J., Washburn L. R., Wiley B. B. Stimulation of mouse lymphocytes by a mitogen derived from Mycoplasma arthritidis. V. A small basic protein from culture supernatants is a potent T cell mitogen. J Immunol. 1986 Sep 1;137(5):1581–1589. [PubMed] [Google Scholar]
  3. Choi Y. W., Kotzin B., Herron L., Callahan J., Marrack P., Kappler J. Interaction of Staphylococcus aureus toxin "superantigens" with human T cells. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8941–8945. doi: 10.1073/pnas.86.22.8941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Choi Y., Kappler J. W., Marrack P. A superantigen encoded in the open reading frame of the 3' long terminal repeat of mouse mammary tumour virus. Nature. 1991 Mar 21;350(6315):203–207. doi: 10.1038/350203a0. [DOI] [PubMed] [Google Scholar]
  5. Cunningham B. C., Bass S., Fuh G., Wells J. A. Zinc mediation of the binding of human growth hormone to the human prolactin receptor. Science. 1990 Dec 21;250(4988):1709–1712. doi: 10.1126/science.2270485. [DOI] [PubMed] [Google Scholar]
  6. Dellabona P., Peccoud J., Kappler J., Marrack P., Benoist C., Mathis D. Superantigens interact with MHC class II molecules outside of the antigen groove. Cell. 1990 Sep 21;62(6):1115–1121. doi: 10.1016/0092-8674(90)90388-u. [DOI] [PubMed] [Google Scholar]
  7. Fischer H., Dohlsten M., Lindvall M., Sjögren H. O., Carlsson R. Binding of staphylococcal enterotoxin A to HLA-DR on B cell lines. J Immunol. 1989 May 1;142(9):3151–3157. [PubMed] [Google Scholar]
  8. Fraser J. D. High-affinity binding of staphylococcal enterotoxins A and B to HLA-DR. Nature. 1989 May 18;339(6221):221–223. doi: 10.1038/339221a0. [DOI] [PubMed] [Google Scholar]
  9. Gascoigne N. R., Ames K. T. Direct binding of secreted T-cell receptor beta chain to superantigen associated with class II major histocompatibility complex protein. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):613–616. doi: 10.1073/pnas.88.2.613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gorga J. C., Horejsí V., Johnson D. R., Raghupathy R., Strominger J. L. Purification and characterization of class II histocompatibility antigens from a homozygous human B cell line. J Biol Chem. 1987 Nov 25;262(33):16087–16094. [PubMed] [Google Scholar]
  11. Herman A., Labrecque N., Thibodeau J., Marrack P., Kappler J. W., Sekaly R. P. Identification of the staphylococcal enterotoxin A superantigen binding site in the beta 1 domain of the human histocompatibility antigen HLA-DR. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9954–9958. doi: 10.1073/pnas.88.22.9954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Janeway C. A., Jr, Yagi J., Conrad P. J., Katz M. E., Jones B., Vroegop S., Buxser S. T-cell responses to Mls and to bacterial proteins that mimic its behavior. Immunol Rev. 1989 Feb;107:61–88. doi: 10.1111/j.1600-065x.1989.tb00003.x. [DOI] [PubMed] [Google Scholar]
  13. Marrack P., Kappler J. The staphylococcal enterotoxins and their relatives. Science. 1990 May 11;248(4956):705–711. doi: 10.1126/science.2185544. [DOI] [PubMed] [Google Scholar]
  14. Mollick J. A., Cook R. G., Rich R. R. Class II MHC molecules are specific receptors for staphylococcus enterotoxin A. Science. 1989 May 19;244(4906):817–820. doi: 10.1126/science.2658055. [DOI] [PubMed] [Google Scholar]
  15. Scheuber P. H., Golecki J. R., Kickhöfen B., Scheel D., Beck G., Hammer D. K. Skin reactivity of unsensitized monkeys upon challenge with staphylococcal enterotoxin B: a new approach for investigating the site of toxin action. Infect Immun. 1985 Dec;50(3):869–876. doi: 10.1128/iai.50.3.869-876.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Scholl P., Diez A., Mourad W., Parsonnet J., Geha R. S., Chatila T. Toxic shock syndrome toxin 1 binds to major histocompatibility complex class II molecules. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4210–4214. doi: 10.1073/pnas.86.11.4210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Stelma G. N., Jr, Bergdoll M. S. Inactivation of staphylococcal enterotoxin A by chemical modification. Biochem Biophys Res Commun. 1982 Mar 15;105(1):121–126. doi: 10.1016/s0006-291x(82)80019-3. [DOI] [PubMed] [Google Scholar]
  18. White J., Herman A., Pullen A. M., Kubo R., Kappler J. W., Marrack P. The V beta-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell. 1989 Jan 13;56(1):27–35. doi: 10.1016/0092-8674(89)90980-x. [DOI] [PubMed] [Google Scholar]

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