title: Inhibition by chloroquine of the class II major histocompatibility complex-restricted presentation of endogenous antigens varies according to the cellular origin of the antigen-presenting cells, the nature of the T-cell epitope, and the responding T cell.
abstract: Chloroquine treatment of antigen-presenting cells (APC) was explored as a tool to investigate the processing pathway for major histocompatibility complex (MHC) class II-restricted presentation of the endogenous secreted hen egg lysozyme (HEL) and transmembrane measles virus haemagglutinin (HA). A 72-hr pretreatment of the APC with 25 microM chloroquine blocked the presentation of the HEL(52-61) T-cell epitope generated from endogenous HEL to the I-Ak-restricted 3A9 T-cell hybridoma by MHC class II-transfected L cells expressing the invariant chain (Ii). The presentation of exogenously added HEL peptides was not affected. Under the same conditions, no inhibition of the presentation of HEL(106-116) to the I-Ed-restricted G28 high-avidity T-cell hybridoma, nor of HA when synthesized by L cells, was observed. When B-lymphoid APC were used, inhibition was observed in every case with a low number of B APC pretreated for 48 hr with chloroquine prior to the T-cell stimulation test. Moreover, addition of chloroquine to untreated B APC during the T-cell stimulation assay was sufficient to inhibit completely the presentation of HEL(106-116) to the B10.D24.42 low avidity T-cell hybridoma. Altogether these studies suggest that an apparent resistance of endogenous Ag presentation to chloroquine inhibition may not necessarily indicate the existence of a non-endosomal pathway but may be due to the nature of the T-cell epitope, to the use of 'non-professional' APC such as L cells, to the use of T cells of high avidity, and to high amounts of pre-existing MHC class II-peptide complexes expressed by the APC. We demonstrate here that, at least in conventional APC such as B cells, class II-restricted presentation of both endogenous secreted HEL and transmembrane HA involves an endosomal pathway.
authors.affiliation: Department of Microbiology and Molecular Genetics, UCLA.
authors.forename: S
authors.initials: S
authors.lastname: Lombard-Platlet
authors.forename: P
authors.initials: P
authors.lastname: Bertolino
authors.forename: H
authors.initials: H
authors.lastname: Deng
authors.forename: D
authors.initials: D
authors.lastname: Gerlier
authors.forename: C
authors.initials: C
authors.lastname: Rabourdin-Combe
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D000938:Antigen-Presenting Cells / Q000187:drug effects; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D005347:Fibroblasts / Q000276:immunology; D006389:Hemagglutinins, Viral / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D009113:Muramidase / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
chemical_list: D000939:Epitopes; D006389:Hemagglutinins, Viral; D000949:Histocompatibility Antigens Class II; D002738:Chloroquine; D009113:Muramidase