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Association of Fc?RIIa (CD32a) with lipid rafts regulates ligand binding activity

Association of Fc?RIIa (CD32a) with lipid rafts regulates ligand binding activity
Association of Fc?RIIa (CD32a) with lipid rafts regulates ligand binding activity
Binding of Igs to myeloid cells via FcR is a key event in the control of innate and acquired immunity. FcRIIa (CD32a) is a receptor for multivalent IgG expressed predominantly by myeloid cells, and its association with microdomains rich in cholesterol and sphingolipids, termed as lipid rafts, has been reported to be essential for efficient signaling. However, for many myeloid cell types, ligand binding to CD32a is suppressed by as yet undefined mechanisms. In this study, we have examined the role of CD32a-lipid raft interactions in the regulation of IgG binding to CD32a. Disruption of lipid raft structure following depletion or sequestration of membrane cholesterol greatly inhibited CD32a-mediated IgG binding. Furthermore, specific CD32a mutants, which show reduced association with lipid rafts (A224S and C241A), displayed decreased levels of IgG binding compared with wild-type CD32a. In contrast, constitutively lipid raft-associated CD32a (GPI-anchored CD32a) exhibited increased capacity for IgG binding compared with the full-length transmembrane CD32a. Our findings clearly suggest a major role for lipid rafts in the regulation of IgG binding and, more specifically, that suppression of CD32a-mediated IgG binding in myeloid cells is achieved by receptor exclusion from lipid raft membrane microdomains.
0022-1767
8026 -8036
Bournazos, Stylianos
58ffee0f-b4aa-468f-ab3d-1b26213169b6
Hart, Simon P.
ad94068b-8bdb-4f82-86cf-365e638fb607
Chamberlain, Luke H.
719a8e9a-3eaf-4e07-9b54-e6b9c585964e
Glennie, M.J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Dransfield, Ian
8e3377ad-39ad-4560-92b7-acaac9c27d0a
Bournazos, Stylianos
58ffee0f-b4aa-468f-ab3d-1b26213169b6
Hart, Simon P.
ad94068b-8bdb-4f82-86cf-365e638fb607
Chamberlain, Luke H.
719a8e9a-3eaf-4e07-9b54-e6b9c585964e
Glennie, M.J.
9f6f0eff-4560-48c2-80cd-0ec116110ded
Dransfield, Ian
8e3377ad-39ad-4560-92b7-acaac9c27d0a

Bournazos, Stylianos, Hart, Simon P., Chamberlain, Luke H., Glennie, M.J. and Dransfield, Ian (2009) Association of Fc?RIIa (CD32a) with lipid rafts regulates ligand binding activity. The Journal of Immunology, 182, 8026 -8036. (doi:10.4049/jimmunol.0900107).

Record type: Article

Abstract

Binding of Igs to myeloid cells via FcR is a key event in the control of innate and acquired immunity. FcRIIa (CD32a) is a receptor for multivalent IgG expressed predominantly by myeloid cells, and its association with microdomains rich in cholesterol and sphingolipids, termed as lipid rafts, has been reported to be essential for efficient signaling. However, for many myeloid cell types, ligand binding to CD32a is suppressed by as yet undefined mechanisms. In this study, we have examined the role of CD32a-lipid raft interactions in the regulation of IgG binding to CD32a. Disruption of lipid raft structure following depletion or sequestration of membrane cholesterol greatly inhibited CD32a-mediated IgG binding. Furthermore, specific CD32a mutants, which show reduced association with lipid rafts (A224S and C241A), displayed decreased levels of IgG binding compared with wild-type CD32a. In contrast, constitutively lipid raft-associated CD32a (GPI-anchored CD32a) exhibited increased capacity for IgG binding compared with the full-length transmembrane CD32a. Our findings clearly suggest a major role for lipid rafts in the regulation of IgG binding and, more specifically, that suppression of CD32a-mediated IgG binding in myeloid cells is achieved by receptor exclusion from lipid raft membrane microdomains.

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Published date: 15 June 2009

Identifiers

Local EPrints ID: 149173
URI: https://eprints.soton.ac.uk/id/eprint/149173
ISSN: 0022-1767
PURE UUID: c5a7f259-678e-4947-8790-8039b31a3d26

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Date deposited: 30 Apr 2010 09:07
Last modified: 17 Jul 2019 00:02

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