Structural homology of mite profilins to plant profilins is not indicative of allergic cross-reactivity.

Structural and allergenic characterization of mite profilins has not been previously pursued to a similar extent as plant profilins. Here, we describe structures of profilins originating from Tyrophagus putrescentiae (registered allergen Tyr p 36.0101) and Dermatophagoides pteronyssinus (here termed Der p profilin), which are the first structures of profilins from Arachnida. Additionally, the thermal stabilities of mite and plant profilins are compared, suggesting that the high number of cysteine residues in mite profilins may play a role in their increased stability. We also examine the cross-reactivity of plant and mite profilins as well as investigate the relevance of these profilins in mite inhalant allergy. Despite their high structural similarity to other profilins, mite profilins have low sequence identity with plant and human profilins. Subsequently, these mite profilins most likely do not display cross-reactivity with plant profilins. At the same time the profilins have highly conserved poly(l-proline) and actin binding sites.

Microscopic Menaces: The Impact of Mites on Human Health.

Mites are highly prevalent arthropods that infest diverse ecological niches globally. Approximately 55,000 species of mites have been identified but many more are yet to be discovered. Of the ones we do know about, most go unnoticed by humans and animals. However, there are several species from the Acariformes superorder that exert a significant impact on global human health. House dust mites are a major source of inhaled allergens, affecting 10-20% of the world's population; storage mites also cause a significant allergy in susceptible individuals; chiggers are the sole vectors for the bacterium that causes scrub typhus; Demodex mites are part of the normal microfauna of humans and their pets, but under certain conditions populations grow out of control and affect the integrity of the integumentary system; and scabies mites cause one of the most common dermatological diseases worldwide. On the other hand, recent genome sequences of mites provide novel tools for mite control and the development of new biomaterial with applications in biomedicine. Despite the palpable disease burden, mites remain understudied in parasitological research. By better understanding mite biology and disease processes, researchers can identify new ways to diagnose, manage, and prevent common mite-induced afflictions. This knowledge can lead to improved clinical outcomes and reduced disease burden from these remarkably widespread yet understudied creatures.

Role of Small Molecule Ligands in IgE-Mediated Allergy.

PURPOSE OF REVIEW: A significant fraction of allergens bind small molecular ligands, and many of these compounds are classified as lipids. However, in most cases, we do not know the role that is played by the ligands in the allergic sensitization or allergic effector phases. RECENT FINDINGS: More effort is dedicated toward identification of allergens' ligands. This resulted in identification of some lipidic compounds that can play active immunomodulatory roles or impact allergens' molecular and allergic properties. Four allergen families (lipocalins, NPC2, nsLTP, and PR-10) are among the best characterized in terms of their ligand-binding properties. Allergens from these four families are able to bind many chemically diverse molecules. These molecules can directly interact with human immune system and/or affect conformation and stability of allergens. While there is more data on the allergens and their small molecular ligands, we are just starting to understand their role in allergy.

Current status of structural studies of proteins originating from Arachnida.

Arthropods from class Arachnida constitute a large and diverse group with over 100,000 described species, and they are sources of many proteins that have a direct impact on human health. Despite the importance of Arachnida, few proteins originating from these organisms have been characterized in terms of their structure. Here we present a detailed analysis of Arachnida proteins that have their experimental structures determined and deposited to the Protein Data Bank (PDB). Our results indicate that proteins represented in the PDB are derived from a small number of Arachnida families, and two-thirds of Arachnida proteins with experimental structures determined are derived from organisms belonging to Buthidae, Ixodidae, and Theraphosidae families. Moreover, 90% of the deposits come from just a dozen of Arachnida families, and almost half of the deposits represent proteins originating from only fifteen different species. In summary, our analysis shows that the structural analysis of proteins originating from Arachnida is not only limited to a small number of the source species, but also proteins from this group of animals are not extensively studied. However, the interest in Arachnida proteins seems to be increasing, which is reflected by a significant increase in the related PDB deposits during the last ten years.

Human IgE monoclonal antibody recognition of mite allergen Der p 2 defines structural basis of an epitope for IgE cross-linking and anaphylaxis in vivo.

Immunoglobulin E (IgE) antibody is a critical effector molecule for adaptive allergen-induced immune responses, which affect up to 40% of the population worldwide. Allergens are usually innocuous molecules but induce IgE antibody production in allergic subjects. Allergen cross-linking of IgE bound to its high affinity receptor (FcεRI) on mast cells and basophils triggers release of histamine and other mediators that cause allergic symptoms. Little is known about the direct allergen-IgE antibody interaction due to the polyclonal nature of serum IgE and the low frequency of IgE-producing B cells in blood. Here, we report the X-ray crystal structure of a house dust mite allergen, Der p 2, in complex with Fab of a human IgE monoclonal antibody (mAb) isolated by hybridoma technology using human B cells from an allergic subject. This IgE mAb, 2F10, has the correct pairing of heavy and light chains as it occurs in vivo. Key amino acids forming the IgE epitope on Der p 2 were identified. Mutation of these residues ablated their functional ability to cross-link IgE in a mouse model of passive systemic anaphylaxis. These analyses revealed an important conformational epitope associated with the IgE antibody repertoire to a major mite allergen.