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-term therapy for atopic diseases will have to rely, for the time being, on passive 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 epsilonRI. Therefore, the epitopes recognized by such antibodies could have vaccine potential.


OBJECTIVE
To determine the epitope specificity of one such human IgG anti-IgE antibody.


METHODS
A 15-mer phage-peptide library was used to establish the epitope specificity 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 or PSP), was present in all 18 phage-peptides that have been sequenced. This common motif was found to be within the human epsilon chain sequence Ser341-Thr355 near the N-terminus of the C epsilon3 domain. According to the human Fc epsilon 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 rational design of a suitable peptide immunogen (vaccine) for boosting the production of protective autoanti-IgE antibodies.
Shakib
F
F
Division of Molecular and Clinical Immunology, University of Nottingham, Faculty of Medicine & Health Sciences, Nottingham, NG7 2UH, United Kingdom.
Hooi
D S
DS
Smith
S J
SJ
Furmonaviciene
R
R
Sewell
H F
HF
D020816:Amino Acid Motifs / Q000276:immunology*; D001249:Asthma / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology* / Q000302:isolation & purification; D001435:Bacteriophages; D002846:Chromatography, Affinity; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D019151:Peptide Library; D016133:Polymerase Chain Reaction
D001323:Autoantibodies; D017931:DNA Primers; D000939:Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; D019151:Peptide Library; D007073:Immunoglobulin E