HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dissanayake, S. K. Articles by Ostrand-Rosenberg, S. Search for Related Content PubMed PubMed Citation Articles by Dissanayake, S. K. Articles by Ostrand-Rosenberg, S.

Presentation of Endogenously Synthesized MHC Class II-Restricted Epitopes by MHC Class II Cancer Vaccines Is Independent of Transporter Associated with Ag Processing and the Proteasome¹

Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250

Cell-based vaccines consisting of invariant chain-negative tumor cells transfected with syngeneic MHC class II (MHC II) and costimulatory molecule genes are prophylactic and therapeutic agents for the treatment of murine primary and metastatic cancers. Vaccine efficacy is due to direct presentation of endogenously synthesized, MHC II-restricted tumor peptides to CD4⁺ T cells. Because the vaccine cells lack invariant chain, we have hypothesized that, unlike professional APC, the peptide-binding groove of newly synthesized MHC II molecules may be accessible to peptides, allowing newly synthesized MHC II molecules to bind peptides that have been generated in the proteasome and transported into the endoplasmic reticulum via the TAP complex. To test this hypothesis, we have compared the Ag presentation activity of multiple clones of TAP-negative and TAP-positive tumor cells transfected with I-A^k genes and the model Ag hen egg white lysozyme targeted to the endoplasmic reticulum or cytoplasm. Absence of TAP does not diminish Ag presentation of three hen egg white lysozyme epitopes. Likewise, cells treated with proteasomal and autophagy inhibitors are as effective APC as untreated cells. In contrast, drugs that block endosome function significantly inhibit Ag presentation. Coculture experiments demonstrate that the vaccine cells do not release endogenously synthesized molecules that are subsequently endocytosed and processed in endosomal compartments. Collectively, these data indicate that vaccine cell presentation of MHC II-restricted endogenously synthesized epitopes occurs via a mechanism independent of the proteasome and TAP complex, and uses a pathway that overlaps with the classical endosomal pathway for presentation of exogenously synthesized molecules.

Related articles in The JI:

IN THIS ISSUE

The JI 2005 174: 1773-1774. [Full Text]  

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]

				O. Demirel, Z. Waibler, U. Kalinke, F. Grunebach, S. Appel, P. Brossart, A. Hasilik, R. Tampe, and R. Abele Identification of a Lysosomal Peptide Transport System Induced during Dendritic Cell Development J. Biol. Chem., December 28, 2007; 282(52): 37836 - 37843. [Abstract] [Full Text] [PDF]

				L. Mortara, P. Castellani, R. Meazza, G. Tosi, A. De Lerma Barbaro, F. A. Procopio, A. Comes, L. Zardi, S. Ferrini, and R. S. Accolla CIITA-Induced MHC Class II Expression in Mammary Adenocarcinoma Leads to a Th1 Polarization of the Tumor Microenvironment, Tumor Rejection, and Specific Antitumor Memory. Clin. Cancer Res., June 1, 2006; 12(11): 3435 - 3443. [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]