A high-affinity natural autoantibody from human cord blood defines a physiologically relevant epitope on the FcepsilonRIalpha.

Bobrzynski, Tomasz; Fux, Michaela; Vogel, Monique; Stadler, Michael B; Stadler, Beda M; Miescher, Sylvia M (2005). A high-affinity natural autoantibody from human cord blood defines a physiologically relevant epitope on the FcepsilonRIalpha. Journal of immunology, 175(10), pp. 6589-6596. American Association of Immunologists 10.4049/jimmunol.175.10.6589

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Natural Abs represent the indigenous immune repertoire and are thus present at birth and persist throughout life. Previously, human autoantibodies to the alpha domain of the high-affinity IgE receptor (FcepsilonRIalpha) have been isolated from Ab libraries derived from normal donors and patients with chronic urticaria. To investigate whether these anti-FcepsilonRIalpha 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 FcepsilonRIalpha had the same sequence. This single IgM Ab, named CBMalpha8, was strictly in germline configuration and had high affinity and functional in vitro anaphylactogenic activity. Inhibition experiments indicated an overlapping epitope on the FcepsilonRIalpha recognized by both CBMalpha8 and the previously isolated anti-FcepsilonRIalpha Abs from autoimmune and healthy donors. This common epitope on FcepsilonRIalpha coincides with the binding site for IgE. Affinity measurements demonstrated the presence of Abs showing CBMalpha8-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-FcepsilonRIalpha Abs are rendered less likely to compete with IgE for binding to FcepsilonRIalpha.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology [discontinued]
UniBE Contributor:	Fux, Michaela
Subjects:	600 Technology > 610 Medicine & health 500 Science
ISSN:	0022-1767
Publisher:	American Association of Immunologists
Language:	English
Submitter:	Dr. Michaela Fux
Date Deposited:	07 Jul 2015 14:30
Last Modified:	05 Dec 2022 14:48
Publisher DOI:	10.4049/jimmunol.175.10.6589
PubMed ID:	16272313
URI:	https://boris.unibe.ch/id/eprint/70133