PubMed · 3048626
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B Guerin, R D Watson. 1988. Skin tests.. https://doi.org/10.1007/bf02914939
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Sensitization to indoor allergens, especially those of the house dust mite, is strongly correlated with the development of asthma. We report the tertiary structure of the major house dust mite allergen, Der p 2, determined by NMR methods. The structure of Der p 2 is a beta-barrel and is composed of two three-stranded antiparallel beta-pleated sheets. This arrangement of beta-strands is similar to the immunoglobulin fold with respect to the orientation of the two sheets and the interactions of the strands. However, the three-dimensional structure of Der p 2 aligns equivalently with a number of proteins from different families within the immunoglobulin superfamily. The structural homology with the highest significance score from analysis by DALI is to Der f 2. Although Der p 2 and Der f 2 are 87% identical in amino acid sequence, they align in three dimensions rather poorly (4.85 A RMSD; Z-score, 8.58). This unexpected finding is likely due to the different solution conditions used during structure determination by NMR for both proteins. While the structural comparisons did not elucidate a clear homologue for the function of Der p 2 in mites, we report that Der p 2 is sequentially homologous to esr16. This is a protein from moths that is expressed coincident with molting. Thus, this homology has important ramifications for the study of mite allergy. The structure of Der p 2 provides a useful tool in the design of recombinant immunotherapeutics for the group 2 allergens.
The Brassica pollen allergen Bra r 1 belongs to a new family of Ca2+-binding proteins, characterized by the presence of two potential EF-hand calcium-binding domains. Disruption of these EF-hand motifs by amino acid substitutions demonstrated that both domains of Bra r 1 constitute functional Ca2+-binding sites. Calcium-binding deficient mutants displayed significantly reduced IgE-binding activity. Injection of these mutated Bra r 1 variants into a murine model system showed that mouse IgG raised against the mutants recognized native Bra r 1 in Brassica pollen extracts suggesting the potential use of the engineered allergens for effective immunotherapy.
IL-5 production in vivo plays a unique role in the production, activation, and localization of eosinophils in a variety of allergic conditions. The current paradigm suggests that allergen-specific Th2 cells are the main source for the IL-5 production. The experiments outlined in this work, however, suggest that in vivo production of IL-5 by NK cells can separately influence eosinophil-associated inflammatory responses. Specifically, a mouse model of allergic inflammation was used in which C57BL/6 mice were immunized and challenged with a short ragweed Ag extract, known to induce a selective eosinophilia within the peritoneal cavity. Peritoneal lavage fluids from these mice also contained increased numbers of T cells and NK cells, as well as significantly elevated levels of IL-4, IL-5, and IFN-gamma. Flow-cytometric analysis of cytokine-producing cells in peritoneal lavage fluid revealed increased numbers of IL-5-producing cells in both T cell and NK cell populations following allergen exposure. Depletion of NK cells by treatment with NK1.1 Abs selectively reduced the number of infiltrating eosinophils by more than 50%. Moreover, the inhibition of the infiltration of eosinophils was accompanied by a complete loss of IL-5-producing NK cells and significantly reduced levels of peritoneal lavage fluid IL-5, whereas the number of IL-5-producing T cells was not affected. Thus, the results presented in this study provide clear evidence for a novel immunoregulatory function of NK cells in vivo, promoting allergen-induced eosinophilic inflammatory responses by the production of IL-5.