Comparative molecular modelling identifies a common putative IgE epitope on cysteine protease allergens of diverse sources

Authors


Dr Shakib Division of Molecular and Clinical Immunology, Faculty of Medicine and Health Sciences, Queen's Medical Centre, Nottingham, NG7 2UH, UK.

Abstract

Background

Previous approaches for studying common allergenic epitopes have mainly focused on sequence comparisons, which unfortunately yield little or no information on the shape of the epitope which is the most important determinant of cross-reactivity.

Objectives

The aim of this study was to investigate the structural basis for cross-reactivity between a previously identified immunodominant epitope of the house dust mite allergen Der p 1 (Leu147-Gln160) and the corresponding epitopes on other allergens that are either taxonomically closely related (i.e. cysteine proteases of other mite species) or representing evolutionary conserved structures (i.e. plant, human and parasite cysteine proteases).

Methods

We carried out comparative molecular modelling on a range of cysteine proteases, including those of other mite species (Der f 1 and Eur m 1), human (cathepsins B, K, L, S and O), plants (papain, chymopapain and actinidin) and parasites (cruzain, cathepsin l-like Leishmania protease, Entamoeba ACP1 protease and Schistosoma Q26534, Q11003 and cathepsin L proteases).

Results

Our study shows that all the cysteine proteases investigated here display an epitope corresponding to that previously identified on Der p 1, but with varying shapes and degree of accessibility. It appears that the core of the epitope on these homologous cysteine proteases consists of a centrally located conserved Tyr residue flanked on either sides by accessible amino acids.

Conclusion

Therefore, these cysteine proteases seem to use similar accessible structures, which may form the basis for the rational design of generic epitope-directed treatment strategies for controlling allergic diseases.

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