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dc.contributor.authorLepage, Stéphanie
dc.contributor.authorLapointe, Réjean
dc.date.accessioned2006-08-14T19:58:35Z
dc.date.available2006-08-14T19:58:35Z
dc.date.issued2006-02-15
dc.identifier.citationLepage, S. and R. Lapointe. 2006. Melanosomal targeting sequences from gp100 are essential for MHC class II-restricted endogenous epitope presentation and mobilization to endosomal compartments. Can. Res. 66:2423-2432.en
dc.identifier.urihttp://hdl.handle.net/1866/159
dc.description.sponsorshipR.L. is the recipient of a « Fond pour la recherché en santé du Québec » scholarship. This work was supported by grants from the Canadian Institutes of Health Research (CIHR) and from « La fondation du CHUM ».en
dc.format.extent2053316 bytes
dc.format.mimetypeapplication/pdf
dc.publisherHighWire Press (American Association for Cancer Research)en
dc.subjectgp100; antigen presentationen
dc.subjectMHC class II compartments (MIIC); CD4+ T lymphocytes, endosomal traffickingen
dc.titleMelanosomal targeting sequences from gp100 are essential for MHC class II-restricted endogenous epitope presentation and mobilization to endosomal compartmentsen
dc.typeArticleen
dc.contributor.affiliationUniversité de Montréal. Faculté de médecine. Département de médecinefr
dcterms.abstractCD4+ T lymphocytes play an important role in CD8+ T cell-mediated responses against tumors. Considering that about 20% of melanomas express major histocompatibility complex (MHC) class II, it is plausible that concomitant antigenic presentation by MHC class I and class II complexes shapes positive (helper T cells) or negative (regulatory T cells) anti-tumor responses. Interestingly, gp100, a melanoma antigen, can be presented by both MHC class I and class II when expressed endogenously, suggesting that it can reach endosomal/MHC class II compartments (MIIC). Here, we demonstrated that the gp100 putative amino-terminal signal sequence and the last 70 residues in carboxy-terminus, are essential for MIIC localization and MHC class II presentation. Confocal microscopy analyses confirmed that gp100 was localized in LAMP-1+ endosomal/MIIC. Gp100-targeting sequences were characterized by deleting different sections in the carboxy-terminus (residues 590 to 661). Transfection in 293T cells, expressing MHC class I and class II molecules, revealed that specific deletions in carboxy-terminus resulted in decreased MHC class II presentation, without effects on MHC class I presentation, suggesting a role in MIIC trafficking for these deleted sections. Then, we used these gp100-targeting sequences to mobilize the green fluorescent protein (GFP) to endosomal compartments, and to allow MHC class II and class I presentation of minimal endogenous epitopes. Thus, we concluded that these specific sequences are MIIC targeting motifs. Consequently, these sequences could be included in expression cassettes for endogenously expressed tumor or viral antigens to promote MHC class II and class I presentation and optimize in vivo T cell responses, or as an in vitro tool for characterization of new MHC class II epitopes.en
dcterms.languageengen
UdeM.VersionRioxxVersion acceptée / Accepted Manuscript


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