IngentaConnect Immune response modulation by recombinant peptides expressed in v...

Authors: SVIRSHCHEVSKAYA, E. V.¹; ALEKSEEVA, L.¹; MARCHENKO, A.²; VISKOVA, N.¹; ANDRONOVA, T. M.¹; BENEVOLENSKII, S. V.²; KURUP, V. P.³

Source: Clinical & Experimental Immunology, Volume 127, Number 2, February 2002 , pp. 199-205(7)

Publisher: Blackwell Publishing

Abstract:

SUMMARY

Aspergillus fumigatus, a ubiquitous fungus, is implicated in the pathogenesis of a number of clinically different allergic diseases in man, including allergic broncopulmonary aspergillosis. Peptide-based immunotherapy may offer an alternative treatment strategy for the management of allergic disease. The objective of this study was to alter the allergen-specific immune response using dominant T cell epitopes of a major A. fumigatus allergen, Asp f2, expressed in yeast as virus-like particles (VLP). The T cell epitopes of Asp f2, recognized in mice with an H-2^d background, were determined by producing T-cell hybridomas. Two dominant T cell epitopes, aa60-71 and aa235-249, were identified and expressed in a yeast VLP system. To induce tolerance VLP-peptides were injected subcutaneously into mice previously immunized with recombinant Asp f2. The T cell immune response was abrogated totally in 3 weeks following a single injection of VLP but was restored 2 months later following intranasal antigen exposure. T-cell depletion resulted in the reduction of 20-30% of all antigen-specific immunoglobulin classes. Thus, recombinant peptides expressed in the VLP system can be used successfully in the modulation of Asp f2-induced immune response in mice, although a single administration is not sufficient to maintain a state of tolerance for a long period of time.

Keywords: allergy; Aspergillus fumigatus; immunotherapy peptide-induced tolerance; virus-like particle

Document Type: Research article

DOI: 10.1046/j.1365-2249.2002.01776.x

Affiliations: 1: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, RAS, 2: State Research Institute for Genetics and Selection of Industrial Microorganisms, Moscow, Russia and 3: Departments of Paediatrics and Medicine, The Medical Collage of Wisconsin, Milwaukee, and the VA Medical Center, Milwaukee, WI, USA

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Immune response modulation by recombinant peptides expressed in virus-like particles