Structure, Antigenic Determinants of Some Clinically Important Insect Allergens: Chironomid Hemoglobins

Abstract

Determination of the molecular structure and properties of allergens that elicit severe immediate-type hypersensitivity diseases in humans and a knowledge of the structure of their antibody-binding sites should provide new insight into the pathogenetic mechanisms of allergic diseases. Monomeric and homodimeric hemoglobins (CTT I to X) have been identified as potent allergenic components of Chironomidae, a family of Diptera. Immunologic investigations of peptides of three of these hemoglobins (CTT IV, CTT VI, and CTT VIII) showed that human antibodies of the E and G classes recognize at least two different sites within each molecule. Individual hemoglobin peptides were aligned with homologous regions of chironomid hemoglobin CTT III, whose tertiary structure has been determined by x-ray analysis at a resolution of 1.4 angstroms. The antigenic site CTT IV(91 to 101) showed the following characteristics: (i) seven polar or hydroxylated amino acids, from a total of eleven, occupying predominantly superficial regions; (ii) the property of linkage to other molecules by hydrogen bonds or solvent clusters; and (iii) high thermal mobility factors. In contrast, peptide CTT IV(102 to 108), which does not bind human antibodies, contained no polar amino acids and had low thermal mobility factors. These results support the idea that the antigenicity of clinically relevant proteins is related to regions with a predominance of polar amino acids and with low energy barriers between different conformations, which allow high flexibility, including site-specific adaptation in antibody binding.

Trematode Myoglobins, Functional Molecules with a Distal Tyrosine

“…A similar high antigenic character of globins is observed for the Hbs/Mbs of the nematodes where the pigment is found in the excretory/ secretory products of Trichostrongylus colubriformis and Nippostrongylus brasiliensis (18 -20). The extracellular Hbs of Ascaris suum and Chironomus thummi thummi are also documented as potent allergens (21,22). The purpose of the high antigenic character of the Hbs/Mbs of the parasite and their occurrence in the excretory/secretory products is unknown.…”

Structure and Epitopes of Chi t 1.01

“…Various algorithms of epitope prediction exist but they are mostly not better than random. However, the N terminus of the insect allergen Chi t 1.01 (hemoglobin component of Chironomus thummi [1]) was predicted to contain B and T cell epitopes [2, 3]. These predictions could be confirmed experimentally.…”

Crystallization and Preliminary Diffraction Data of a Major Pollen Allergen

“…Preliminary structural data on a few allergens based on modeling studies have been published (18,19); NMR solution structures have been reported for two allergens from ragweed (20,21), but this is the first report concerning the crystallization of a grass pollen allergen. Such studies are possible due to the availability of recombinant allergens in sufficient amounts, and our experience leads us to suggest that crystallographic techniques may make a substantial contribution to allergy research.…”