Peptides et protéines recombinantes modifiées de la PLA2 d'abeille

Abstract

Recent advances in the understanding of the mechanisms of specific allergen immunotherapy have revealed that T cell epitopes containing molecules that are devoid of reactivity for specific IgE are suitable candidates for specific immunotherapy. This led us to design peptides and recombinant proteins derived from the major bee venom allergen PLA2 that possess such a characteristic. T cells epitopes have been delineated by means of a bank of HLA II proteins that are representative of the diversity of the immune system of the European population. Using this information, we demonstrate that four 18-residue peptides contain the majority of these T cell epitopes. Recombinant forms have been constructed by successive addition of restricted mutations and one deletion outside the T cell epitope-containing regions. One of these peptides containing all the modifications exhibited very little reactivity with IgE from bee venom-allergic patients. In contrast, this mutant peptide was recognized equally as well as the native form of the protein by murine T cells. Moreover, in the mouse it activates T cells specific for both forms. It displays a native-like 3D structure but is more flexible. Altogether, these results allow us to propose in this same allergenic system a set of peptides and one recombinant protein as candidates for specific immunotherapy of patients allergic to bee venom.