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Internalization of iscom-borne antigens and presentation under MHC class I or class II restriction

Villacres, MC; Behboudi, S; Nikkila, T; Lovgren-Bengtsson, K; Morein, B; (1998) Internalization of iscom-borne antigens and presentation under MHC class I or class II restriction. CELL IMMUNOL , 185 (1) 30 - 38.

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Abstract

Exogenous nonreplicating antigens (Ag) incorporated into into immunostimulating complexes (iscoms) induce CTE responses under MHC class I restriction. A requirement for inducing CTL responses is that the Ag is delivered to the cytosol of antigen-presenting cells (APC), a route restricted to endogenously produced Ag. To investigate the mechanisms by which iscoms elicit MHC class I-restricted responses, the intracellular distribution of influenza virus envelope proteins incorporated in iscoms (flu-iscoms) or in micelles (flu-micelles) was studied in vitro using murine peritoneal cells (PEC). Ultrathin sections of cells pulsed with biotinylated flu-iscoms or flu-micelles were analyzed by electron microscopy after detection of the biotin label by reaction with streptavidin-gold. PEC pulsed with flu-iscoms showed a pattern of scattered gold particles distributed in clear and dense vesicles as well as in the intracellular space but not associated with. organelles. In cells pulsed with flu-micelles, Ag was also detected in most cellular compartments but at a considerably lower concentration. The intracellular distribution of particulate Ag in iscom or micelle form was confirmed by lysis and differential centrifugation of Ag-pulsed APC. Furthermore, P815 cells pulsed with flu-iscoms were lysed by specific immune effecters showing that time iscom-AE; was processed and presented by class I-expressing APC. flu-iscoms were internalized about 50-fold more efficiently than ovalbumin iscoms (ova-iscoms) suggesting that the nature of the protein and/or the presence of cellular receptors are important factors influencing the capacity of APC to take up iscom-borne proteins. PEC accounted for the most active internalization of iscom-borne Ag, although splenic dendritic cells and B cells also took up flu-iscoms with remarkable efficiency. (C) 1998 Academic Press.

Type:Article
Title:Internalization of iscom-borne antigens and presentation under MHC class I or class II restriction
Keywords:iscoms, antigen internalization, antigen presentation, MHC class I, CYTOTOXIC T-CELLS, IMMUNE-STIMULATING COMPLEXES, B SURFACE-ANTIGEN, DENDRITIC CELLS, IMMUNOSTIMULATING COMPLEXES, LYMPHOCYTE ACTIVITY, PARTICULATE ANTIGENS, EXOGENOUS ANTIGENS, VIRUS, RESPONSES
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)

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