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. 1992 May 1;175(5):1301–1305. doi: 10.1084/jem.175.5.1301

Sequences in both class II major histocompatibility complex alpha and beta chains contribute to the binding of the superantigen toxic shock syndrome toxin 1

PMCID: PMC2119222  PMID: 1569399

Abstract

Class II major histocompatibility complex (MHC) molecules present peptides derived from processed antigen to antigen-specific CD4- positive T cells. In addition, class II molecules bind with high affinity another class of antigens, termed superantigens. T cell stimulation by superantigens depends almost exclusively on the V beta segment expressed by the T cell receptor (TCR). Mapping of the superantigen binding site on class II molecules should provide valuable information on how MHC and TCR molecules interact. Recombinant mouse I- A class II molecules expressed on transfected L cells were analyzed for their ability to bind the toxic shock syndrome toxin 1. Polymorphic residues in the alpha helices of both the alpha and beta chains of I-A contributed to quantitative toxin binding, suggesting that the toxin binds to either a combinatorial or a conformational site on class II MHC molecules.

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Selected References

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  1. Acha-Orbea H., McDevitt H. O. The first external domain of the nonobese diabetic mouse class II I-A beta chain is unique. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2435–2439. doi: 10.1073/pnas.84.8.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
  3. Braunstein N. S., Germain R. N. Allele-specific control of Ia molecule surface expression and conformation: implications for a general model of Ia structure-function relationships. Proc Natl Acad Sci U S A. 1987 May;84(9):2921–2925. doi: 10.1073/pnas.84.9.2921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Braunstein N. S., Germain R. N., Loney K., Berkowitz N. Structurally interdependent and independent regions of allelic polymorphism in class II MHC molecules. Implications for Ia function and evolution. J Immunol. 1990 Sep 15;145(6):1635–1645. [PubMed] [Google Scholar]
  5. Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
  6. Carlsson R., Fischer H., Sjögren H. O. Binding of staphylococcal enterotoxin A to accessory cells is a requirement for its ability to activate human T cells. J Immunol. 1988 Apr 15;140(8):2484–2488. [PubMed] [Google Scholar]
  7. Chintagumpala M. M., Mollick J. A., Rich R. R. Staphylococcal toxins bind to different sites on HLA-DR. J Immunol. 1991 Dec 1;147(11):3876–3881. [PubMed] [Google Scholar]
  8. 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]
  9. Fleischer B., Schrezenmeier H. T cell stimulation by staphylococcal enterotoxins. Clonally variable response and requirement for major histocompatibility complex class II molecules on accessory or target cells. J Exp Med. 1988 May 1;167(5):1697–1707. doi: 10.1084/jem.167.5.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Herman A., Croteau G., Sekaly R. P., Kappler J., Marrack P. HLA-DR alleles differ in their ability to present staphylococcal enterotoxins to T cells. J Exp Med. 1990 Sep 1;172(3):709–717. doi: 10.1084/jem.172.3.709. [DOI] [PMC free article] [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., Chalupny J., Conrad P. J., Buxser S. An external stimulus that mimics Mls locus responses. J Immunogenet. 1988 Feb-Jun;15(1-3):161–168. doi: 10.1111/j.1744-313x.1988.tb00418.x. [DOI] [PubMed] [Google Scholar]
  13. Karp D. R., Long E. O. Identification of HLA-DR1 beta chain residues critical for binding staphylococcal enterotoxins A and E. J Exp Med. 1992 Feb 1;175(2):415–424. doi: 10.1084/jem.175.2.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Karp D. R., Teletski C. L., Scholl P., Geha R., Long E. O. The alpha 1 domain of the HLA-DR molecule is essential for high-affinity binding of the toxic shock syndrome toxin-1. Nature. 1990 Aug 2;346(6283):474–476. doi: 10.1038/346474a0. [DOI] [PubMed] [Google Scholar]
  15. Kwok W. W., Thurtle P., Nepom G. T. A genetically controlled pairing anomaly between HLA-DQ alpha and HLA-DQ beta chains. J Immunol. 1989 Dec 1;143(11):3598–3601. [PubMed] [Google Scholar]
  16. 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]
  17. Oi V. T., Jones P. P., Goding J. W., Herzenberg L. A., Herzenberg L. A. Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol. 1978;81:115–120. doi: 10.1007/978-3-642-67448-8_18. [DOI] [PubMed] [Google Scholar]
  18. Pontzer C. H., Russell J. K., Johnson H. M. Structural basis for differential binding of staphylococcal enterotoxin A and toxic shock syndrome toxin 1 to class II major histocompatibility molecules. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):125–128. doi: 10.1073/pnas.88.1.125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Scholl P. R., Diez A., Geha R. S. Staphylococcal enterotoxin B and toxic shock syndrome toxin-1 bind to distinct sites on HLA-DR and HLA-DQ molecules. J Immunol. 1989 Oct 15;143(8):2583–2588. [PubMed] [Google Scholar]
  20. Scholl P. R., Diez A., Karr R., Sekaly R. P., Trowsdale J., Geha R. S. Effect of isotypes and allelic polymorphism on the binding of staphylococcal exotoxins to MHC class II molecules. J Immunol. 1990 Jan 1;144(1):226–230. [PubMed] [Google Scholar]
  21. Scholl P. R., Sekaly R. P., Diez A., Glimcher L. H., Geha R. S. Binding of toxic shock syndrome toxin-1 to murine major histocompatibility complex class II molecules. Eur J Immunol. 1990 Sep;20(9):1911–1916. doi: 10.1002/eji.1830200907. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. 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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