Lipocalins are one of the groups of allergens derived from domestic animals with clinical importance for the development of allergic responses. They have been characterized in different animals. With allergenic capacity characterized, little is known about the epitopes involved in allergic responses. Here, potential antigenic regions involved in cross-reactivity among lipocalins were explored through bioinformatics tools. The amino acid sequences of several lipocalins from different domestic animals (mouse, dog, cat, bull, hamster, horse and pig) were used to determine the degree of kinship by phylogenetic studies. Groups with highest phylogenetic relation were obtained by using MEGA software. 3D models of lipocalins not reported in the protein data bank were modeled by homology to identify potential antigenic regions compromised in the cross-reactivity of this group of allergens. The alignment of the entire database of allergenic lipocalins and the inferred maximum likelihood tree segregate lipocalins into five monophyletic clades (referenced here as A, B, C, D and E). According to the multiple pairing analyzes, group C (Fel d 4, Rat n 1 and Equ c 1) showed the highest degree of identity among their amino acid sequences (58%). The analysis of conserved and exposed residues showed that group C shares three antigenic regions that could potentially contribute to its cross-reactivity. Potential antigenic sites were identified for the generation of cross-reactivity between the different lipocalins analyzed in this study. These studies support the need to carry out directed mutagenesis tests to confirm their relevance in the allergenic capacity of lipocalins.
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