Abstract
Desensitising therapy for allergic diseases has changed little over almost a century of practice. Administration of increasing doses of extracts of allergen source material has been shown to be reproducibly effective when patients are carefully selected and appropriate concentrations of allergen employed. However, specific immunotherapy is limited by the interaction of specific IgE with allergen, leading to a relatively high frequency of adverse events including anaphylaxis and death. Several strategies have been developed to tackle this issue. Most of these rely on reducing the allergenicity of the treatment, whilst maintaining the immunogenicity. The use of short, synthetic peptide sequences corresponding to T-cell epitopes from the allergen has been shown to modify surrogate markers of allergy including cutaneous responses to allergen challenge and ex vivo parameters of T-cell activation. This review discusses recent advances in our understanding of the mechanisms and potential efficacy of this form of therapy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Reference
Kay AB (2001) Allergy and allergic diseases. First of two parts. N Engl J Med 344:30–37
Kay AB (2001) Allergy and allergic diseases. Second of two parts. N Engl J Med 344:109–113
Noon L (1911) Prophylactic inoculation against hay fever. Lancet I:1572–1573
Marsh DG, Norman PS, Roebber M, et al (1981) Studies on allergoids from naturally occurring allergens. III. Preparation of ragweed pollen allergoids by aldehyde modification in two steps. J Allergy Clin Immunol 68:449–459
Ferreira F, Ebner C, Kramer B, et al (1998) Modulation of IgE reactivity of allergens by site-directed mutagenesis: potential use of hypoallergenic variants for immunotherapy. FASEB J 12:231–242
Creticos PS, Eiden JJ, Balcer S, et al (2000) Immunostimulatory oligonucleotides conjugated to Amb a 1: safety, skin test reactivity and basophil histamine release. J Allergy Clin Immunol 105:S70
Creticos PS, Balcer S, Schroeder JT, et al (2001) Initial immunotherapy trial to explore the safety, tolerability and immunogenicity of subcutaneous injections of an Amb a 1 immunostimulatory oligonucleotide conjugate (Aic) in ragweed allergic adults. J Allergy Clin Immunol 107:S216
Norman PS, Ohman JL, Long AA, et al (1996) Treatment of cat allergy with T-cell reactive peptides. Am J Respir Crit Care Med 154:1623–1628
Pene J, Desroches A, Paradis L, et al (1998) Immunotherapy with Feld1 peptides decreases IL-4 release by peripheral blood T cells of patients allergic to cats. J Allergy Clin Immunol 102:571–578
Simons FE, Imada M, Li Y, et al (1996) Feld1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects. Int Immunol 8:1937–1945
Maguire P, Nicodemus C, Robinson D, et al (1999) The safety and efficacy of allervax cat in cat allergic patients. Clin Immunol 93:222–231
Oldfield WL, Kay AB, Larche M (2001) Allergen-derived T cell peptide-induced late asthmatic reactions precede the induction of antigen-specific hyporesponsiveness in atopic allergic asthmatic subjects. J Immunol 167:1734–1739
Oldfield WL, Larche M, Kay AB (2002) Effect of T-cell peptides derived from Feld1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial. Lancet 360 47–53
Muller U, Akdis CA, Fricker M, et al (1998) Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. J Allergy Clin Immunol 101:747–754
Fellrath JM, Kettner A, Dufour N, et al (2003) Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: results of a phase I trial. J Allergy Clin Immunol 111:854–861
Haselden BM, Kay AB, Larche M (1999) Immunoglobulin E-independent major histocompatibility complex-restricted T cell peptide epitope-induced late asthmatic reactions. J Exp Med 189:1885–1894
Vidard L, Colarusso LJ, Benacerraf B (1994) Specific T-cell tolerance may be preceded by a primary response. Proc Natl Acad Sci U S A 91:5627–5631
Webb S, Morris C, Sprent J (1990) Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell 63:1249–1256
Hoyne GF, Askonas BA, Hetzel C, et al (1996) Regulation of house dust mite responses by intranasally administered peptide: transient activation of CD4+ T cells precedes the development of tolerance in vivo. Int Immunol 8:335–342
Marcotte GV, Braun CM, Norman PS, et al (1998) Effects of peptide therapy on ex vivo T-cell responses. J Allergy Clin Immunol 101:506–513
Santambrogio L, Sato AK, Fischer FR, et al (1999) Abundant empty class II MHC molecules on the surface of immature dendritic cells. Proc Natl Acad Sci U S A 96:15050–15055
Santambrogio L, Sato AK, Carven GJ, et al (1999) Extracellular antigen processing and presentation by immature dendritic cells. Proc Natl Acad Sci U S A 96:15056–15061
Hakonarson H, Maskeri N, Carter C, et al (1999) Regulation of TH1- and TH2-type cytokine expression and action in atopic asthmatic sensitized airway smooth muscle. J Clin Invest 103:1077–1087
Ati TR, Oldfield WLG, Higashi N, et al (2003) Late asthmatic reactions induced by inhalation of allergen-derived T-cell peptides. Am J Resp Crit Care Med DOI: 10.1164/rccm.200305-690C
Acknowledgements
The authors are indebted Dr. Mimi Haselden, Dr. Bill Oldfield, Dr. Clare Alexander, Dr. Runa Ali, Dr. Douglas Robinson, Ms. Karen Shirley and Ms. Justine Arbery. This research was funded by the National Asthma Campaign and the Medical Research Council, UK.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Barry Kay, A., Larché, M. Allergen immunotherapy with cat allergen peptides. Springer Semin Immun 25, 391–399 (2004). https://doi.org/10.1007/s00281-003-0146-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00281-003-0146-y