Dendritic cell maturation enhances CD8+ T-cell responses to exogenous antigen via a proteasome-independent mechanism of major histocompatibility complex class I loading

Robson, N. C., Beacock-Sharp, H., Donachie, A. M. and Mowat, A. M. (2003) Dendritic cell maturation enhances CD8+ T-cell responses to exogenous antigen via a proteasome-independent mechanism of major histocompatibility complex class I loading. Immunology, 109(3), pp. 374-383. (doi: 10.1046/j.1365-2567.2003.01664.x) (PMID:12807483)

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Abstract

Immune stimulating complexes (ISCOMS) containing the saponin adjuvant Quil A are vaccine adjuvants that induce a wide range of immune responses in vivo, including strong class I major histocompatibility complex (MHC) -restricted cytotoxic T-lymphocyte activity. However, the antigen-presenting cell responsible for the induction of these responses has not been characterized. Here we have investigated the role of dendritic cells (DC) in the priming of antigen-specific CD8+ T cells in vitro by ISCOMS containing ovalbumin. Resting bone marrow DC pulsed with ovalbumin ISCOMS efficiently prime resting CD8+ T cells through a mechanism that is transporter associated with antigen processing (TAP) dependent, but independent of CD40 ligation and CD4+ T-cell help. Lipopolysaccharide-induced maturation of DC markedly enhances their ability to prime CD8+ T cells through a mechanism which is also independent of CD4+ T-cell help, but is dependent on CD40 ligation. Furthermore, DC maturation revealed a TAP-independent mechanism of CD8+ T-cell priming. Our results also show that class I MHC-restricted presentation of ovalbumin in ISCOMS by DC is sensitive to chloroquine and brefeldin A but insensitive to lactacystin. We suggest that DC may be the principal antigen-presenting cells responsible for the priming of CD8+ T cells by ISCOMS in vivo and that targeting these vectors to activated DC may enhance their presentation via a novel pathway of class I antigen processing.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Robson, Dr Neil and Mowat, Professor Allan and Donachie, Ms Anne Marie
Authors: Robson, N. C., Beacock-Sharp, H., Donachie, A. M., and Mowat, A. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Immunology
Publisher:Wiley-Blackwell Publishing Ltd.
ISSN:0019-2805
ISSN (Online):1365-2567

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
266071MUCIMM Mucosal Immunization - Cluster ProjectAllan MowatEuropean Commission (EC)QLK2-CT-1999-00III -IMMUNOLOGY
229411Novel strategies in mucosal adjuvant construction based on the immuno-modulating properties of cholera toxin and ISCOMSAllan MowatEuropean Commission (EC)CT98-0505III -IMMUNOLOGY