Identification of peptide motifs recognized by a human IgG autoanti-IgE antibody using a phage display library

Background The potential of murine monoclonal anti-IgE antibodies as long-t erm therapy for atopic diseases will have to rely, for the time being, on p assive antibody administration. There is therefore considerable interest in developing a peptide-based vaccine for active immunization to elicit long- term protective anti-IgE antibodies in the patient. It has been shown that some human IgG autoanti-IgE antibodies have the ability to partially block the binding of IgE to Fc receptors such as Fc epsilon RI. Therefore, the ep itopes recognized by such antibodies could have vaccine potential. Objective To determine the epitope specificity of one such human IgG anti-I gE antibody. Methods A 15-mer phage-peptide library was used to establish the epitope sp ecificity of an IgG anti-IgE antibody isolated from the serum of an asthma patient. Results The SRPSP sequence, or part of it (i.e. RPS, RPSP, SPS of PSP), was present in all 18 phage-peptides that have been sequenced. This common mot if was found to be within the human epsilon chain sequence Ser341-Thr355 ne ar the N-terminus of the C epsilon 3 domain. According to the human Fc epsi lon model, the most accessible residues in this sequence are Arg342, Ile350 , Arg351, Lys352 and Ser353. Conclusions The present data should provide the molecular basis for the rat ional design of a suitable peptide immunogen (vaccine) for boosting the pro duction of protective autoanti-IgE antibodies.