HLA-DQ8 is a predisposing molecule for detergent enzyme subtilisin BPN′-induced hypersensitivity

Several million individuals are exposed to agents in the workplace associated with atopy and asthma. Detergent enzymes have been implicated in occupationally induced hypersensitivity. However, the genetic susceptibility and T cell responses to detergent enzymes are undefined. We generated and used H...

Full description

Saved in:

Bibliographic Details
Published in:	Clinical Immunology Vol. 117; no. 3; pp. 302 - 315
Main Authors:	Xue, Ailing, Chapoval, Svetlana P., Finn, Elizabeth S., Chowdhary, Vaidehi R., Marietta, Eric V., Gaffey, Thomas A., Pursifull, Alex C., David, Chella S.
Format:	Journal Article
Language:	English
Published:	San Diego, CA Elsevier Inc 01-12-2005 Elsevier
Subjects:	Allergy Animals Antigens Biological and medical sciences Bronchoalveolar Lavage Fluid - cytology Bronchoalveolar Lavage Fluid - immunology Cytokines Detergent Disease Models, Animal Enzyme Eosinophils Epitopes Fundamental and applied biological sciences. Psychology Fundamental immunology Genetic Predisposition to Disease HLA-DQ Antigens - biosynthesis HLA-DQ Antigens - genetics HLA-DR Antigens - biosynthesis HLA-DR Antigens - genetics Hypersensitivity - genetics Hypersensitivity - immunology Immunization Immunoglobulin E - immunology Immunoglobulin G - immunology Immunopathology Knockout Lung - anatomy & histology Lung - pathology Lymphocytes - cytology Macrophages - cytology Medical sciences Mice Mice, Transgenic Occupational Diseases - immunology Peptides Subtilisins - administration & dosage Subtilisins - immunology Subtilisins - pharmacology Transgenic Allergy Antigens Detergent Peptides Cytokines Enzyme Transgenic Epitopes Knockout Eosinophils HLA-System Antigenic determinant Major histocompatibility system Granulocyte Immunology Gene HLA-A-Locus Class I histocompatibility antigen Immunopathology Serine endopeptidases Hypersensitivity Cytokine Subtilisin Eosinophil Peptidases Hydrolases Mutation
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Several million individuals are exposed to agents in the workplace associated with atopy and asthma. Detergent enzymes have been implicated in occupationally induced hypersensitivity. However, the genetic susceptibility and T cell responses to detergent enzymes are undefined. We generated and used HLA-DQ6, -DQ8, -DR2, -DR3, and -DR4 transgenic mice to examine the immune and inflammatory components involved in the response to the detergent enzyme subtilisin BPN′. Based on in vitro and in vivo studies, for the first time, we present evidence that DQ8 is a strong susceptibility marker for BPN′-induced hypersensitivity. Only DQ8 mice showed consistent T cell responses to five immunodominant regions of BPN′ comprising peptides #14 to 16, 36–37, 42–43, 62–63, and 80–81. The DQ8 mice also developed allergic eosinophilic inflammatory reactions in the airways following intranasal instillations of this enzyme. The DQ8 mice also responded to BPN′ with a significant IgG1 and IgE production. We propose that the HLA Class II tg mice are useful for understanding allergenic responses to enzymes in humans, screening of allergenic and immunogenic properties of detergent enzymes, and for the development of modified enzymes to maintain efficient detergent qualities without allergic properties.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1521-6616 1521-7035 1365-2567
DOI:	10.1016/j.clim.2005.08.003