House dust mites (Dermatophagoides) are an important cause of allergic diseases such as perennial rhinitis, asthma and atopic dermatitis and the two principal species, D. pteronyssinus and D. farinae have been found in homes in many parts of the United States.
The aims of this project are to determine the primary structures and the antigenic relationships between the two major groups of dust mite allergens: the 24kd Group I allergens (der p I, Der f I, and Der m I) and the 15kd Group II allergens (Der p II and Der f II). The amino acid sequences of these allergens will be determined using the combined approaches of peptide sequencing (Edman degradation and tandem mass spectrometry) and cDNA cloning in Lambda gt 10. Structural homology between each allergen and other proteins of known amino acid sequence will be compared. Binding of murine monoclonal antibodies and human IgG and IgE antibodies to both allergen groups will be compared by antigen binding radioimmunoassays. Epitope mapping studies will be carried out by comparing antibody binding to denatured allergens, chemically modified allergens and peptide fragments.
The aim will be to determine the repertoire of B cell epitopes, whether they are sequential or topographic and which amino acid residues provide the contact points for antibody binding. Murine antibody responses to Group I allergens will be compared in several inbred strains using different immunization regimes to investigate whether modes of immunization which affect isotype expression also influence epitope specificity. Human T cell responses to the Group I and II allergens will be compared n in vitro cell culture systems using peripheral blood T cells from mite allergic patients. Synthetic peptides will be used to stimulate T cell clones and to identify T cell epitopes. The role of antigen presenting cells in processing allergens prior to presentation to T cells will also be investigated. This proposal provides a systematic approach to studying the molecular and antigenic structure of major dust mite allergens. These studies should result in greater understanding of factors which influence both humoral and cellular immune responses to mite allergens. They should also provide further knowledge as to why these allergens are such a common cause of rhinitis, asthma and atopic dermatitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI024687-02
Application #
3454065
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Vailes, L D; Li, Y; Bao, Y et al. (1994) Fine specificity of B-cell epitopes on Felis domesticus allergen I (Fel d I): effect of reduction and alkylation or deglycosylation on Fel d I structure and antibody binding. J Allergy Clin Immunol 93:22-33
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Arruda, L K; Platts-Mills, T A; Longbottom, J L et al. (1992) Aspergillus fumigatus: identification of 16, 18, and 45 kd antigens recognized by human IgG and IgE antibodies and murine monoclonal antibodies. J Allergy Clin Immunol 89:1166-76
Morgenstern, J P; Griffith, I J; Brauer, A W et al. (1991) Amino acid sequence of Fel dI, the major allergen of the domestic cat: protein sequence analysis and cDNA cloning. Proc Natl Acad Sci U S A 88:9690-4
Pollart, S M; Smith, T F; Morris, E C et al. (1991) Environmental exposure to cockroach allergens: analysis with monoclonal antibody-based enzyme immunoassays. J Allergy Clin Immunol 87:505-10

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