Allergens of Blomia tropicalis: An Overview of Recombinant Molecules

Abstract

Allergic diseases are considered a major problem for healthcare systems in both developed and developing countries. House dust mites are well-known triggers of allergic manifestations. While the Dermatophagoides genus is widely distributed globally, Blomia tropicalis is the most prominent mite species in the tropical and subtropical regions of the world. Over the last decades, an increase in sensitization rates to B. tropicalis has been reported, leading to increased research efforts on Blomia allergens. In fact, 8 new allergens have been identified and characterized to different degrees. Here, we provide an overview of recent developments concerning the identification and production of recombinant Blomia allergens, as well as their structural and immunological characterization. Although considerable progress has been achieved, detailed molecule-based studies are still needed to better define the clinical relevance of Blomia allergens. Thus, the establishment of a well-standardized and fully characterized panel of allergens remains a challenge for the development of better diagnosis and therapy of allergic diseases induced by B. tropicalis.

Keywords: Blomia tropicalis; Cross-reactivity; Immunoglobulin E epitopes; Recombinant allergens; Secondary structure; T-cell epitopes; Three-dimensional structure.

Fig. 1

Tertiary structures of Blomia tropicalis allergens. Structures for Blo t 5, 8, 12, 19, and 21 were taken from the PDB database [111]. For the remaining allergens, models were calculated by comparative modeling using MODELLER software [51]. In case of nuclear magnetic resonance PDB entries, the model scoring function of MAESTRO was employed [112] to select a representative template structure. With MODELLER, 5 model variants were generated. The displayed structures always represent the model with the best MAESTRO score. Molecular graphics were created with UCSF Chimera [113]. Unless denoted otherwise, active site residues are shown in red and T-cell epitopes in purple. B-cell epitopes are represented as orange surface patches. In the case of comparative modeling, the UniProt code of the target allergen sequence, the organism of the template structure, and its PDB code are given in parentheses, otherwise only the PDB code is shown. a Blo t 1 (A1KXI0 modeled on 1XKG from Dermatophagoides pteronyssinus). The orange ribbon represents the pro-peptide, which blocks the access to the CYS-HIS-ASN catalytic site b Blo t 2 (Q1M2P1 modeled on 1KTJ from D. pteronyssinus). c Blo t 3 (Q8I916 modeled on 1GQD from Fusarium oxysporum) is a potential serine type endopeptidase with a SER-HIS-ASP catalytic triad. d Blo t 4 (A1KXI2 modeled on 1PIF from Sus scrofa) is a potential α-amylase, with ASP and GLU at the active site. e Blo t 5 (2MEY), T-cell and B-cell epitopes as described in other studies [42, 44, 47] are depicted. f Blo t 6 (A1KXI3 modeled on 2F91 from Astacus leptodactylus) is also a potential serine type endopeptidase. g Blo t 8 (4Q5N), chain A (in green), and chain B (in orange). h Blo t 10 and Blo t 11 are expected to contain extensive coiled coil regions. Here we show a coiled coil region from tropomyosin (3U59) from Gallus gallus. How the coils fold up in space cannot be reliably modeled on the currently known PDB entries. i Chitin-binding domain of Blo t 12 (2MFK). j Blo t 13 (Q17284 modeled on 2A0A from D. farinae) is a fatty-acid-binding protein. k Blo t 19 (2MFJ). l Blo t 21 (2LM9); the depicted residues have been shown to be a part of B-cell epitopes [79].