Hypoallergenic variants of the major latex allergen Hev b 6.01 retaining human T lymphocyte reactivity
Data(s) |
01/01/2004
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Resumo |
Hev b 6.01 is a major allergen of natural rubber latex with sensitization of 70–86% of latex glove-allergic subjects. Recently, we mapped the immunodominant T cell sites of Hev b 6.01 to the highly IgE-reactive hevein (Hev b 6.02) domain. Hev b 6.01 contains 14 cysteine residues with multiple disulphide bridges stabilizing tertiary conformation. With the goal of a standardized specific immunotherapy we developed hypoallergenic Hev b 6.01 mutants by site-directed mutagenesis of selected cysteine residues (3, 12, 17, and 41) within the Hev b 6.02 domain. Peptides corresponding to the Hev b 6.02 domain of two of the mutants were also synthesized. These mutants and peptide variants showed markedly decreased or ablated latex-allergic patient serum IgE binding by immunoblotting and ELISA. Basophil activation testing confirmed markedly decreased activation with successive cysteine substitutions of the mutants and complete abrogation with the Hev b 6.02 (Cys 3, 12, 17, 41 Ala) peptide. Retention of T cell reactivity is crucial for effective specific immunotherapy and all mutants and peptide variants maintained their latex-specific T cell reactivity. The ablated allergenicity but retained T cell reactivity of the Hev b 6.02 (Cys 3, 12, 17, 41 Ala) peptide suggests this peptide is a suitable candidate for inclusion in a latex immunotherapy preparation.<br /> |
Identificador | |
Idioma(s) |
eng |
Publicador |
American Association of Immunologists |
Relação |
http://dro.deakin.edu.au/eserv/DU:30019592/suphioglu-hypoallergenicvariants-2004.pdf http://www.jimmunol.org/cgi/reprint/173/9/5872?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=Drew%2C+AC&searchid=1&FIRSTINDEX=0&sortspec=relevance&volume=173&firstpage=5872&resourcetype=HWCIT |
Direitos |
2004, The American Association of Immunologists, Inc. |
Tipo |
Journal Article |