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2010-10-31Zeitschriftenartikel DOI: 10.1371/journal.ppat.1001154
Direct Visualization of Peptide/MHC Complexes at the Surface and in the Intracellular Compartments of Cells Infected In Vivo by Leishmania major
dc.contributor.authorMuraille, Eric
dc.contributor.authorGounon, Pierre
dc.contributor.authorCazareth, Julie
dc.contributor.authorHoebeke, Johan
dc.contributor.authorLippuner, Christoph
dc.contributor.authorDavalos-Misslitz, Ana
dc.contributor.authorAebischer, Toni
dc.contributor.authorMuller, Sylviane
dc.contributor.authorGlaichenhaus, Nicolas
dc.contributor.authorMougneau, Evelyne
dc.date.accessioned2018-05-07T14:14:58Z
dc.date.available2018-05-07T14:14:58Z
dc.date.created2010-11-29
dc.date.issued2010-10-31none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/recvrhcSpMa3g/PDF/20lXBC3QEnBOQ.pdf
dc.identifier.urihttp://edoc.rki.de/176904/759
dc.description.abstractProtozoa and bacteria infect various types of phagocytic cells including macrophages, monocytes, dendritic cells and eosinophils. However, it is not clear which of these cells process and present microbial antigens in vivo and in which cellular compartments parasite peptides are loaded onto Major Histocompatibility Complex molecules. To address these issues, we have infected susceptible BALB/c (H-2d) mice with a recombinant Leishmania major parasite expressing a fluorescent tracer. To directly visualize the antigen presenting cells that present parasite-derived peptides to CD4+ T cells, we have generated a monoclonal antibody that reacts to an antigenic peptide derived from the parasite LACK antigen bound to I-Ad Major Histocompatibility Complex class II molecule. Immunogold electron microscopic analysis of in vivo infected cells showed that intracellular I-Ad/LACK complexes were present in the membrane of amastigote-containing phagosomes in dendritic cells, eosinophils and macrophages/monocytes. In both dendritic cells and macrophages, these complexes were also present in smaller vesicles that did not contain amastigote. The presence of I-Ad/LACK complexes at the surface of dendritic cells, but neither on the plasma membrane of macrophages nor eosinophils was independently confirmed by flow cytometry and by incubating sorted phagocytes with highly sensitive LACK-specific hybridomas. Altogether, our results suggest that peptides derived from Leishmania proteins are loaded onto Major Histocompatibility Complex class II molecules in the phagosomes of infected phagocytes. Although these complexes are transported to the cell surface in dendritic cells, therefore allowing the stimulation of parasite-specific CD4+ T cells, this does not occur in other phagocytic cells. To our knowledge, this is the first study in which Major Histocompatibility Complex class II molecules bound to peptides derived from a parasite protein have been visualized within and at the surface of cells that were infected in vivo.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subjectAmino Acid Sequenceeng
dc.subjectAnimalseng
dc.subjectMiceeng
dc.subjectPeptide Fragments/chemistryeng
dc.subjectMice Inbred BALB Ceng
dc.subjectCell Compartmentation/immunologyeng
dc.subjectCell Membrane/immunologyeng
dc.subjectCell Membrane/metabolismeng
dc.subjectCells Culturedeng
dc.subjectFluorescent Antibody Technique/methodseng
dc.subjectHistocompatibility Antigens Class II/immunologyeng
dc.subjectHistocompatibility Antigens Class II/metabolismeng
dc.subjectIntracellular Membranes/metabolismeng
dc.subjectLeishmania major/immunologyeng
dc.subjectLeishmaniasis Cutaneous/immunologyeng
dc.subjectLeishmaniasis Cutaneous/metabolismeng
dc.subjectMice Inbred C3Heng
dc.subjectMice Inbred C57BLeng
dc.subjectMice Inbred NODeng
dc.subjectPeptide Fragments/immunologyeng
dc.subjectPeptide Fragments/metabolismeng
dc.subjectPhagosomes/immunologyeng
dc.subjectPhagosomes/metabolismeng
dc.subject.ddc610 Medizin
dc.titleDirect Visualization of Peptide/MHC Complexes at the Surface and in the Intracellular Compartments of Cells Infected In Vivo by Leishmania major
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-10011626
dc.identifier.doi10.1371/journal.ppat.1001154
dc.identifier.doihttp://dx.doi.org/10.25646/684
local.edoc.container-titlePLoS Pathogens
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001154
local.edoc.container-publisher-namePublic Library of Science
local.edoc.container-volume6
local.edoc.container-issue10
local.edoc.container-year2010

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