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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3199-3205. Prepublished online as a Blood First Edition Paper on December 23, 2004; DOI 10.1182/blood-2004-09-3556. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-09-3556v1 105/8/3199    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dörfel, D. Articles by Brossart, P. Search for Related Content PubMed PubMed Citation Articles by Dörfel, D. Articles by Brossart, P. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Processing and presentation of HLA class I and II epitopes by dendritic cells after transfection with in vitro–transcribed MUC1 RNA Daniela Dörfel, Silke Appel, Frank Grünebach, Markus M. Weck, Martin R. Müller, Annkristin Heine, and Peter Brossart From the Department of Hematology, Oncology and Immunology, University of Tübingen, Germany. RNA transfection of dendritic cells (DCs) was shown to be highly efficient in eliciting CD8+ and CD4+ T-cell responses. However, antigen presentation pathways involved in generation of human leukocyte antigen (HLA) class I and class II peptides have remained elusive. To analyze this we incubated mucin 1 (MUC1) RNA-transfected DCs with compounds known to inhibit HLA class I presentation and used these cells in chromium 51 (51Cr)–release assays. As effectors, we used cytotoxic T lymphocyte (CTL) lines specific for the MUC1 peptides M1.1 and M1.2. We observed that the presentation of HLA-A*02 epitopes is inhibited by brefeldin A and lactacystin. To determine the requirement of a functional transporter associated with antigen processing (TAP), we cotransfected DCs with MUC1 and infected cell peptide 47 (ICP47) RNA. ICP47 could only inhibit the presentation of the M1.1 but not the M1.2 peptide, indicating that this epitope derived from the signal sequence is presented independently of TAP. Cocultivation of MUC1 RNA-transfected DCs with MUC1-specific CD4+ T lymphocytes revealed that the presentation of HLA class II peptides is sensitive to proteasomal inhibitors and brefeldin A. Furthermore, the presentation pathway requires lysosomal and endosomal processing and is mediated by autophagy. Our results demonstrate that the efficient presentation of cytosolic proteins on major histocompatibility complex (MHC) class II combines the proteolytic and lysosomal pathways. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. L. Crotzer and J. S. Blum Autophagy and Its Role in MHC-Mediated Antigen Presentation J. Immunol., March 15, 2009; 182(6): 3335 - 3341. [Abstract] [Full Text] [PDF] Y. Su, G. Carey, M. Maric, and D. W. Scott B Cells Induce Tolerance by Presenting Endogenous Peptide-IgG on MHC Class II Molecules via an IFN-{gamma}-Inducible Lysosomal Thiol Reductase-Dependent Pathway J. Immunol., July 15, 2008; 181(2): 1153 - 1160. [Abstract] [Full Text] [PDF] M. S. Swanson Autophagy: Eating for Good Health J. Immunol., October 15, 2006; 177(8): 4945 - 4951. [Abstract] [Full Text] [PDF] A. Amano, I. Nakagawa, and T. Yoshimori Autophagy in Innate Immunity against Intracellular Bacteria J. 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[Abstract] [Full Text] [PDF] V. L. Crotzer and J. S. Blum Autophagy and intracellular surveillance: Modulating MHC class II antigen presentation with stress PNAS, May 31, 2005; 102(22): 7779 - 7780. [Full Text] [PDF] J. Dengjel, O. Schoor, R. Fischer, M. Reich, M. Kraus, M. Muller, K. Kreymborg, F. Altenberend, J. Brandenburg, H. Kalbacher, et al. From the Cover: Autophagy promotes MHC class II presentation of peptides from intracellular source proteins PNAS, May 31, 2005; 102(22): 7922 - 7927. [Abstract] [Full Text] [PDF]

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