title: MHC class II-peptide complexes in dendritic cell lipid microdomains initiate the CD4 Th1 phenotype.
abstract: We investigated differentiation of CD4 T cells responding to Ag presented by bone marrow-derived dendritic cells (DC) in association with MHC class II (MHC II) molecules. Peptides encapsulated in liposomes opsonized by IgG were taken up by endocytosis. MHC II-peptide-specific T cells responding to this Ag were polarized to a Th1 cytokine profile in a CD40-, CD28-, MyD88-, and IL-12-dependent manner. Th2 responses were obtained from the same transgenic T cell population exposed to the same DC on which MHC-peptide complexes had dispersed for 48 h following uptake of FcR-targeted liposomes. DC that took up the same FcR-targeted liposomes and then were exposed to methyl-beta-cyclodextrin, which chelates cholesterol and dissociates lipid microdomains, also stimulated Th2 differentiation. Incubation of T cells with DC incubated with peptides directly binding to MHC II resulted in Th2 responses, whether or not the DC were coincubated with opsonized liposomes as a maturation stimulus. CD4 Th1 polarization thus appears to depend on MHC II-peptide complex clustering in DC lipid microdomains and the time between peptide loading and T cell encounter.
authors.affiliation: Centre d'Immunologie Institut National de la Santé et de la Recherche Médicale-Centre National de la Recherche Scientifique-Université de la Méditerranée de Marseille-Luminy, Marseille, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Buatois
authors.forename: Marjorie
authors.initials: M
authors.lastname: Baillet
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bécart
authors.forename: Nuala
authors.initials: N
authors.lastname: Mooney
authors.forename: Lee
authors.initials: L
authors.lastname: Leserman
authors.forename: Patrick
authors.initials: P
authors.lastname: Machy
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D003505:Cyclodextrins / Q000737:chemistry; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D016130:Immunophenotyping; D018664:Interleukin-12 / Q000378:metabolism; D008081:Liposomes; D008213:Lymphocyte Activation / Q000276:immunology; D021962:Membrane Microdomains / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009113:Muramidase / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D011961:Receptors, Fc / Q000737:chemistry; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D047392:beta-Cyclodextrins
chemical_list: D003505:Cyclodextrins; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C111388:I-Ak antigen; D008081:Liposomes; D010446:Peptide Fragments; D011961:Receptors, Fc; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D018664:Interleukin-12; C066759:hen egg lysozyme peptide (46-61); D009113:Muramidase