Details

Autor(en) / Beteiligte

• Bobrzynski, Tomasz
• Fux, Michaela
• Vogel, Monique
• Stadler, Michael B.
• Stadler, Beda M.
• Miescher, Sylvia M.

Titel

A High-Affinity Natural Autoantibody from Human Cord Blood Defines a Physiologically Relevant Epitope on the FcεRIα

Ist Teil von

• Journal of Immunology, 2005-11, Vol.175 (10), p.6589-6596

Erscheinungsjahr

2005

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Abstract Natural Abs represent the indigenous immune repertoire and are thus present at birth and persist throughout life. Previously, human autoantibodies to the α domain of the high-affinity IgE receptor (FcεRIα) have been isolated from Ab libraries derived from normal donors and patients with chronic urticaria. To investigate whether these anti-FcεRIα Abs are present in the germline repertoire, we constructed a phage Fab display library from human cord blood, which represents the naive immune repertoire before exposure to exogenous Ags. All isolated clones specific to the FcεRIα had the same sequence. This single IgM Ab, named CBMα8, was strictly in germline configuration and had high affinity and functional in vitro anaphylactogenic activity. Inhibition experiments indicated an overlapping epitope on the FcεRIα recognized by both CBMα8 and the previously isolated anti-FcεRIα Abs from autoimmune and healthy donors. This common epitope on FcεRIα coincides with the binding site for IgE. Affinity measurements demonstrated the presence of Abs showing CBMα8-like specificity, but with a significantly lower affinity in i.v. Ig, a therapeutic multidonor IgG preparation. We propose a hypothesis of escape mutants, whereby the resulting lower affinity IgG anti-FcεRIα Abs are rendered less likely to compete with IgE for binding to FcεRIα.