Skip to main content
NCBI home page
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 Aug 15;89(16):7727–7731. doi: 10.1073/pnas.89.16.7727

T-cell antigen receptor binding sites for the microbial superantigen staphylococcal enterotoxin A.

C H Pontzer 1, M J Irwin 1, N R Gascoigne 1, H M Johnson 1
PMCID: PMC49784  PMID: 1502191

Abstract

We have examined the interaction of the microbial superantigen staphylococcal enterotoxin A (SEA) with peptides corresponding to overlapping regions of the T-cell antigen receptor beta chain variable region V beta 3. SEA is known to stimulate murine T cells bearing certain V beta elements, among them V beta 3. Five peptides were synthesized representing amino acids 1-24, 20-44, 39-60, 57-77, and 74-95 of V beta 3. We demonstrate here that soluble V beta 3-bearing beta chains can bind to a complex of SEA and major histocompatibility complex class II and that the synthetic peptide V beta 3-(57-77) blocked this interaction. The peptide V beta 3-(57-77) also inhibited SEA-induced interferon-gamma production and SEA-induced proliferation of B10.BR spleen cells. Conversely, the peptide corresponding to amino acids 57-77 of V beta 8.2, a V beta element that is not recognized by SEA, decreased staphylococcal enterotoxin C-2-induced proliferation but did not affect SEA-induced proliferation. The peptide inhibition of SEA-induced function was due at least in part to inhibition of V beta 3-bearing T-cell activity, since the percentage of T cells reactive with an anti-V beta 3 monoclonal antibody was significantly reduced by V beta 3-(57-77). These data suggest that the region of V beta 3 encompassing amino acids 57-77 is an area that displays the appropriate sequence and conformation for binding of the SEA molecule and blocking of the resultant interaction with the T-cell antigen receptor.

Full text

PDF
7727

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Callahan J. E., Herman A., Kappler J. W., Marrack P. Stimulation of B10.BR T cells with superantigenic staphylococcal toxins. J Immunol. 1990 Apr 1;144(7):2473–2479. [PubMed] [Google Scholar]
  2. Carlsson R., Sjögren H. O. Kinetics of IL-2 and interferon-gamma production, expression of IL-2 receptors, and cell proliferation in human mononuclear cells exposed to staphylococcal enterotoxin A. Cell Immunol. 1985 Nov;96(1):175–183. doi: 10.1016/0008-8749(85)90349-1. [DOI] [PubMed] [Google Scholar]
  3. Cazenave P. A., Marche P. N., Jouvin-Marche E., Voegtlé D., Bonhomme F., Bandeira A., Coutinho A. V beta 17 gene polymorphism in wild-derived mouse strains: two amino acid substitutions in the V beta 17 region greatly alter T cell receptor specificity. Cell. 1990 Nov 16;63(4):717–728. doi: 10.1016/0092-8674(90)90138-5. [DOI] [PubMed] [Google Scholar]
  4. Chang C. D., Meienhofer J. Solid-phase peptide synthesis using mild base cleavage of N alpha-fluorenylmethyloxycarbonylamino acids, exemplified by a synthesis of dihydrosomatostatin. Int J Pept Protein Res. 1978 Mar;11(3):246–249. doi: 10.1111/j.1399-3011.1978.tb02845.x. [DOI] [PubMed] [Google Scholar]
  5. Chien Y. H., Gascoigne N. R., Kavaler J., Lee N. E., Davis M. M. Somatic recombination in a murine T-cell receptor gene. Nature. 1984 May 24;309(5966):322–326. doi: 10.1038/309322a0. [DOI] [PubMed] [Google Scholar]
  6. Choi Y. W., Herman A., DiGiusto D., Wade T., Marrack P., Kappler J. Residues of the variable region of the T-cell-receptor beta-chain that interact with S. aureus toxin superantigens. Nature. 1990 Aug 2;346(6283):471–473. doi: 10.1038/346471a0. [DOI] [PubMed] [Google Scholar]
  7. Chothia C., Boswell D. R., Lesk A. M. The outline structure of the T-cell alpha beta receptor. EMBO J. 1988 Dec 1;7(12):3745–3755. doi: 10.1002/j.1460-2075.1988.tb03258.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Claverie J. M., Prochnicka-Chalufour A., Bougueleret L. Implications of a Fab-like structure for the T-cell receptor. Immunol Today. 1989 Jan;10(1):10–14. doi: 10.1016/0167-5699(89)90058-3. [DOI] [PubMed] [Google Scholar]
  9. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  10. Fleischer B., Gerardy-Schahn R., Metzroth B., Carrel S., Gerlach D., Köhler W. An evolutionary conserved mechanism of T cell activation by microbial toxins. Evidence for different affinities of T cell receptor-toxin interaction. J Immunol. 1991 Jan 1;146(1):11–17. [PubMed] [Google Scholar]
  11. 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]
  12. Gascoigne N. R. Transport and secretion of truncated T cell receptor beta-chain occurs in the absence of association with CD3. J Biol Chem. 1990 Jun 5;265(16):9296–9301. [PubMed] [Google Scholar]
  13. Gerlier D., Thomasset N. Use of MTT colorimetric assay to measure cell activation. J Immunol Methods. 1986 Nov 20;94(1-2):57–63. doi: 10.1016/0022-1759(86)90215-2. [DOI] [PubMed] [Google Scholar]
  14. Grossman D., Van M., Mollick J. A., Highlander S. K., Rich R. R. Mutation of the disulfide loop in staphylococcal enterotoxin A. Consequences for T cell recognition. J Immunol. 1991 Nov 15;147(10):3274–3281. [PubMed] [Google Scholar]
  15. 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]
  16. Jarpe M. A., Hayes M. P., Russell J. K., Johnson H. M., Russell S. W. Causal association of interferon-gamma with tumor regression. J Interferon Res. 1989 Apr;9(2):239–244. doi: 10.1089/jir.1989.9.239. [DOI] [PubMed] [Google Scholar]
  17. Johnson H. M., Magazine H. I. Potent mitogenic activity of staphylococcal enterotoxin A requires induction of interleukin 2. Int Arch Allergy Appl Immunol. 1988;87(1):87–90. doi: 10.1159/000234654. [DOI] [PubMed] [Google Scholar]
  18. Kappler J. W., Roehm N., Marrack P. T cell tolerance by clonal elimination in the thymus. Cell. 1987 Apr 24;49(2):273–280. doi: 10.1016/0092-8674(87)90568-x. [DOI] [PubMed] [Google Scholar]
  19. Langford M. P., Stanton G. J., Johnson H. M. Biological effects of staphylococcal enterotoxin A on human peripheral lymphocytes. Infect Immun. 1978 Oct;22(1):62–68. doi: 10.1128/iai.22.1.62-68.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Parker J. M., Guo D., Hodges R. S. New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites. Biochemistry. 1986 Sep 23;25(19):5425–5432. doi: 10.1021/bi00367a013. [DOI] [PubMed] [Google Scholar]
  21. Pontzer C. H., Russell J. K., Johnson H. M. Localization of an immune functional site on staphylococcal enterotoxin A using the synthetic peptide approach. J Immunol. 1989 Jul 1;143(1):280–284. [PubMed] [Google Scholar]
  22. Pullen A. M., Bill J., Kubo R. T., Marrack P., Kappler J. W. Analysis of the interaction site for the self superantigen Mls-1a on T cell receptor V beta. J Exp Med. 1991 May 1;173(5):1183–1192. doi: 10.1084/jem.173.5.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pullen A. M., Marrack P., Kappler J. W. The T-cell repertoire is heavily influenced by tolerance to polymorphic self-antigens. Nature. 1988 Oct 27;335(6193):796–801. doi: 10.1038/335796a0. [DOI] [PubMed] [Google Scholar]
  24. Pullen A. M., Wade T., Marrack P., Kappler J. W. Identification of the region of T cell receptor beta chain that interacts with the self-superantigen MIs-1a. Cell. 1990 Jun 29;61(7):1365–1374. doi: 10.1016/0092-8674(90)90700-o. [DOI] [PubMed] [Google Scholar]
  25. Russell J. K., Jarpe M. A., Johnson H. M. Evidence for the alpha-helicity of class II MHC molecular binding sites for the superantigen, staphylococcal enterotoxin A. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1016–1024. doi: 10.1016/0006-291x(92)91833-c. [DOI] [PubMed] [Google Scholar]
  26. Russell J. K., Pontzer C. H., Johnson H. M. The I-A beta b region (65-85) is a binding site for the superantigen, staphylococcal enterotoxin A. Biochem Biophys Res Commun. 1990 Apr 30;168(2):696–701. doi: 10.1016/0006-291x(90)92377-c. [DOI] [PubMed] [Google Scholar]
  27. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES