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. 1993 Nov 1;178(5):1783–1788. doi: 10.1084/jem.178.5.1783

Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of the dominant T cell epitope in naive and sensitized mice

PMCID: PMC2191220  PMID: 8228823

Abstract

Antigen-specific CD4+ T cells play an important role in the allergic immune response to house dust mite (HDM) allergens in humans. The group 1 allergen of Dermatophagoides spp. is a major target antigen in both B and T cell recognition of HDM. In vitro studies have shown that the presentation of peptides to human T cells under appropriate conditions may lead to a state of specific nonresponsiveness. Therefore, to determine if peptides are able to modulate the function of allergen- reactive T cells in vivo, we have used a murine model of T cell recognition of the HDM allergen Der p 1. The results demonstrate that inhalation of low concentrations of peptide containing the major T cell epitope of Der p 1 (residues 111-139), induces tolerance in naive C57BL/6J mice such that they become profoundly unresponsive to an immunogenic challenge with the intact allergen. When restimulated in vitro with antigen, lymph node T cells isolated from tolerant mice secrete very low levels of interleukin 2, proliferative poorly, and are unable to provide cognate help to stimulate specific antibody production. Furthermore, intranasal peptide therapy was able to inhibit an ongoing immune response to the allergen in mice and this has potential implications in the development of allergen-based immunotherapy.

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Selected References

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  1. Challacombe S. J., Tomasi T. B., Jr Systemic tolerance and secretory immunity after oral immunization. J Exp Med. 1980 Dec 1;152(6):1459–1472. doi: 10.1084/jem.152.6.1459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clayton J. P., Gammon G. M., Ando D. G., Kono D. H., Hood L., Sercarz E. E. Peptide-specific prevention of experimental allergic encephalomyelitis. Neonatal tolerance induced to the dominant T cell determinant of myelin basic protein. J Exp Med. 1989 May 1;169(5):1681–1691. doi: 10.1084/jem.169.5.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gammon G., Dunn K., Shastri N., Oki A., Wilbur S., Sercarz E. E. Neonatal T-cell tolerance to minimal immunogenic peptides is caused by clonal inactivation. 1986 Jan 30-Feb 5Nature. 319(6052):413–415. doi: 10.1038/319413a0. [DOI] [PubMed] [Google Scholar]
  4. Greene W. K., Chua K. Y., Stewart G. A., Thomas W. R. Antigenic analysis of group I house dust mite allergens using random fragments of Der p I expressed by recombinant DNA libraries. Int Arch Allergy Appl Immunol. 1990;92(1):30–38. doi: 10.1159/000235220. [DOI] [PubMed] [Google Scholar]
  5. Higgins J. A., Lamb J. R., Marsh S. G., Tonks S., Hayball J. D., Rosen-Bronson S., Bodmer J. G., O'Hehir R. E. Peptide-induced nonresponsiveness of HLA-DP restricted human T cells reactive with Dermatophagoides spp. (house dust mite). J Allergy Clin Immunol. 1992 Nov;90(5):749–756. doi: 10.1016/0091-6749(92)90098-m. [DOI] [PubMed] [Google Scholar]
  6. Holt P. G., Leivers S. Tolerance induction via antigen inhalation: isotype specificity, stability, and involvement of suppressor T cells. Int Arch Allergy Appl Immunol. 1982;67(2):155–160. doi: 10.1159/000233007. [DOI] [PubMed] [Google Scholar]
  7. Holt P. G., McMenamin C. Defence against allergic sensitization in the healthy lung: the role of inhalation tolerance. Clin Exp Allergy. 1989 May;19(3):255–262. doi: 10.1111/j.1365-2222.1989.tb02380.x. [DOI] [PubMed] [Google Scholar]
  8. Hoyne G. F., Callow M. G., Kuo M. C., Thomas W. R. Characterization of T-cell responses to the house dust mite allergen Der p II in mice. Evidence for major and cryptic epitopes. Immunology. 1993 Jan;78(1):65–73. [PMC free article] [PubMed] [Google Scholar]
  9. Kelso A. Frequency analysis of lymphokine-secreting CD4+ and CD8+ T cells activated in a graft-versus-host reaction. J Immunol. 1990 Oct 1;145(7):2167–2176. [PubMed] [Google Scholar]
  10. Miller A., Lider O., Weiner H. L. Antigen-driven bystander suppression after oral administration of antigens. J Exp Med. 1991 Oct 1;174(4):791–798. doi: 10.1084/jem.174.4.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mowat A. M., Strobel S., Drummond H. E., Ferguson A. Immunological responses to fed protein antigens in mice. I. Reversal of oral tolerance to ovalbumin by cyclophosphamide. Immunology. 1982 Jan;45(1):105–113. [PMC free article] [PubMed] [Google Scholar]
  12. O'Hehir R. E., Aguilar B. A., Schmidt T. J., Gollnick S. O., Lamb J. R. Functional inactivation of Dermatophagoides spp. (house dust mite) reactive human T-cell clones. Clin Exp Allergy. 1991 Mar;21(2):209–215. doi: 10.1111/j.1365-2222.1991.tb00832.x. [DOI] [PubMed] [Google Scholar]
  13. O'Hehir R. E., Lamb J. R. Induction of specific clonal anergy in human T lymphocytes by Staphylococcus aureus enterotoxins. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8884–8888. doi: 10.1073/pnas.87.22.8884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. O'Hehir R. E., Yssel H., Verma S., de Vries J. E., Spits H., Lamb J. R. Clonal analysis of differential lymphokine production in peptide and superantigen induced T cell anergy. Int Immunol. 1991 Aug;3(8):819–826. doi: 10.1093/intimm/3.8.819. [DOI] [PubMed] [Google Scholar]
  15. Qin S., Cobbold S. P., Pope H., Elliott J., Kioussis D., Davies J., Waldmann H. "Infectious" transplantation tolerance. Science. 1993 Feb 12;259(5097):974–977. doi: 10.1126/science.8094901. [DOI] [PubMed] [Google Scholar]
  16. Ria F., Chan B. M., Scherer M. T., Smith J. A., Gefter M. L. Immunological activity of covalently linked T-cell epitopes. Nature. 1990 Jan 25;343(6256):381–383. doi: 10.1038/343381a0. [DOI] [PubMed] [Google Scholar]
  17. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  18. Whitacre C. C., Gienapp I. E., Orosz C. G., Bitar D. M. Oral tolerance in experimental autoimmune encephalomyelitis. III. Evidence for clonal anergy. J Immunol. 1991 Oct 1;147(7):2155–2163. [PubMed] [Google Scholar]

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