Abstract:
:Natural anti-cholesterol antibodies (ACHAs) exist in mammalian species, moreover their level sensitively changes in pathological situations, such as atherosclerosis or HIV infection. The conditions of their production and functional role, however, still remained ill defined. Recently we developed IgG3 type monoclonal ACHAs that selectively react with 'clustered cholesterol' of live immune cells, such as membrane microdomains (lipid rafts and caveolas). These antibodies inhibited HIV-1 infection of Th cells and macrophages by remodeling the HIV-1 receptor/coreceptor distribution in the plasma membrane of target cells. As a novel modulatory effect, here we show that the AC8 IgG3 monoclonal anti-cholesterol antibody (mACHA), but not the AC9 IgM mACHA, spontaneously bind to all professional APCs, such as murine macrophages (Mfs) or bone marrow derived dendritic cells (DCs) and B lymphocytes. Upon binding, AC8 mAb remarkably enhanced the efficiency of yeast uptake by macrophages, but not the uptake of OVA-Ig immune complexes by DCs. Binding to B lymphoma APCs, AC8 mAb remodeled their surface membrane by microclustering rafts and recruiting MHC-II and the CD80 costimulators to common microdomains. The modulated APCs induced an enhanced activation signaling (higher Ca(2+)-signals and NFAT1 activation) in Th cells conjugated with them, relative to untreated APCs. The results presented herein highlight the modulatory potential of the IgG3 type AC8 mAb on both innate and adaptive effector cell functions.
journal_name
Immunol Lettjournal_title
Immunology lettersauthors
Izsepi E,Balogh A,Farkas A,Molnar A,Solymos E,Toth EA,Csepanyi-Komi R,Matko Jdoi
10.1016/j.imlet.2012.01.009subject
Has Abstractpub_date
2012-03-30 00:00:00pages
106-15issue
1eissn
0165-2478issn
1879-0542pii
S0165-2478(12)00011-9journal_volume
143pub_type
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