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

Background Previous approaches for studying common allergenic epitopes have mainly focused on sequence comparisons, which unfortunately yield little o r no information on the shape of the epitope which is the most important de terminant of cross-reactivity. Objectives The aim of this study was to investigate the structural basis fo r cross-reactivity between a previously identified immunodominant epitope o f the house dust mite allergen Der p 1 (Leu147-Gln160) and the correspondin g epitopes on other allergens that are either taxonomically closely related (i.e. cysteine proteases of other mite species) or representing evolutiona ry conserved structures (i.e. plant, human and parasite cysteine proteases) . Methods We carried out comparative molecular modelling on a range of cystei ne proteases, including those of other mite species (Der f 1 and fur m 1), human (cathepsins B, K, L, S and O), plants (papain, chymopapain and actini din) and parasites (cruzain, cathepsin L-like Leishmania protease, Entamoeb a ACP 1 protease and Schistosoma Q26534, Q11003 and cathepsin L proteases). Results Our study shows that all the cysteine proteases investigated here d isplay an epitope corresponding to that previously identified on Der p 1, b ut with varying shapes and degree of accessibility. It appears that the cor e of the epitope on these homologous cysteine proteases consists of a centr ally located conserved Tyr residue flanked on either sides by accessible am ino acids. Conclusion Therefore, these cysteine proteases seem to use similar accessib le structures, which may form the basis for the rational design of generic epitope-directed treatment strategies for controlling allergic diseases.