Recherche immunitaire
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Heat Shock Protein-derived peptides as a potential immuno-regulatory vaccine in allergy. “In silico” analysis.

Andrea Pagetta, Giulia Frigo, Elisa Tramentozzi and Paola Finotti

Background Allergic and autoimmune diseases are forms of altered immune responses directed respectively against exogenous and endogenous antigens. A growing body of experimental evidence exists to support a com-mon pathogenetic link between allergy and autoimmunity. Identification of shared antigens might thus be usefully exploited in the therapy of both conditions. The allergy to cat allergens is very common and fre-quently associated with asthma. Sequences of the main cat allergen Fel d1, containing overlapping T cell epitopes that bind to HLA molecules, have been used as an effective allergen-specific peptide vaccine. It has been observed that human proteins identified as cross-reactive auto-antigens with structural homology with environmental allergens often belong to evolutionarily conserved proteins. Heat shock proteins (HSPs) are among the most conserved proteins and some of them have been recog-nized as antigens in autoimmune diseases and also as the main proteins of environmental allergens. We performed an extensive “in silico” analysis to test the hypothesis that the human HSPs Grp94, Grp78, HSP90, HSP71 and HSP60 could show similarity with both Fel d1 and other common allergens, thus serv-ing as a source of peptides in a broad-spectrum allergen-specific immuno-therapy. Results An extensive structural similarity was observed between Fel d1 and sequences of HSP71, Grp78, HSP90 and Grp94. These HSP sequences contained T-cell epitopes with binding capacity to HLA alleles better than that displayed by corresponding similar Fel d1-derived peptides employed so far as therapeutic vac-cines. A significant similarity was also found between these HSP sequences and other aeroallergens, not shared by Fel d1-derived peptides. HLA alleles involved in binding HSP sequences were mostly those as-sociated with an increased predisposition to both allergy and autoimmune diseases. Conclusion Results support the possibility that HSP-derived immuno-dominant epitopes are exploitable as therapeutic peptides in allergies other than cat allergy.