Molecular Structure of Allergens

Abstract

Inhalant allergens attack people in natural, domestic and occupational environments and consist of protein or glycoprotein mixtures, highly purified proteins (MW 5000–80000 Daltons) or low-molecular-weight chemicals. Sensitized subjects develop hypersensitivity reactions to the exposure to extremely low doses.

For Chi 11 component III, an aggressive inhalant insect allergen with known primary and tertiary structures, we studied antigen-antibody interactions (IgE, IgG, mAB) as well as immunogenicity. We mapped Chi 11 component III with natural and synthetic peptides and identified B and T-cell epitopes.

Using a computer display of the 3-D coordinates we localized and verified B-and T-cell epitopes in the tertiary structure.

The B-cell epitope position 1–15 is found at the N-terminal end of the molecule at the beginning of helix A. Epitope 91–101 is located between helices F and G and at the beginning of helix G. Epitope 110–135 is between helices G and H and in helix H.

A good agreement between the secondary structure elements (helices and turns) and the thermal mobility profile with the functional properties of the peptides was found.

We also applied T-cell epitope prediction methods to state T-helper sites on Chi 11 component III. The capacity of tryptic and synthetic peptides to stimulate peripheral blood lymphocytes corresponds well with regions of high alpha am-phipathic score (Berzofsky et al.) and/or the sequence motif according to Rothbard and Taylor.

Furthermore, we studied the immunoresponse to Chi 11 allergen on a genetic basis. The HLA-DRB and -DQB genes were studied in 181 Chi t I-exposed persons of whom 58 showed IgE-mediated sensitization. We used the PCR and hybridisation with 25 sequence specific oligonucleotides to study hypervariable regions of the second exons of DRB genes and DQB genes. DQw1.1 was shown to correlate with the immunoresponse of Chi 11 whereas DQw3 was negatively associated with this hyperreactivity. These associations are significant in non-atopic responders. Our results suggest a different mechanism in the immunoresponse of non-atopic and atopic subjects.

Due to new techniques in molecular genetics and protein chemistry, the primary structures of an increasing number of clinically relevant allergens have been described in recent years. Among them are components of pollen, molds, mites, and animal dander (Table 1). Immunogens inducing type I immune responses show particular structural properties. Their molecular weight (MW) is limited to a small range; approximately 90% of them have a MW of 10–30 kDa. Furthermore, all of them are proteins or glycoproteins. Up to now, few data exist, however, on the 3-D structures of allergens.

Table 1 Highly purified and (partially) characterized allergens.