Structure, antigenic determinants of some clinically important insect allergens: chironomid hemoglobins.
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.
D000485:Allergens / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D002683:Chironomidae / Q000276:immunology*; D004175:Diptera / Q000276:immunology*; D000939:Epitopes / Q000032:analysis*; D006454:Hemoglobins / Q000032:analysis / Q000276:immunology*; D007814:Larva / Q000032:analysis; D008968:Molecular Conformation; D010446:Peptide Fragments / Q000032:analysis; D013696:Temperature
D000485:Allergens; D000939:Epitopes; D006454:Hemoglobins; D010446:Peptide Fragments