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

J. Biol. Chem., Vol. 283, Issue 15, 9957-9965, April 11, 2008

This Article Full Text Full Text (PDF) All Versions of this Article: 283/15/9957    most recent M709574200v1 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 Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shen, X. Z. Articles by Bernstein, K. E. Search for Related Content PubMed PubMed Citation Articles by Shen, X. Z. Articles by Bernstein, K. E. Social Bookmarking                      What's this?

Expression of Angiotensin-converting Enzyme Changes Major Histocompatibility Complex Class I Peptide Presentation by Modifying C Termini of Peptide Precursors^*

From the Department of Pathology, Emory University School of Medicine, Atlanta, Georgia 30322

We recently reported a mouse model called ACE 10/10 in which macrophages overexpress the carboxypeptidase angiotensin-converting enzyme (ACE). These mice have an enhanced inflammatory response to tumors that markedly inhibits tumor growth. Here, we show that ACE modifies the C termini of peptides for presentation by major histocompatibility complex (MHC) class I molecules. The peptide-processing activity of ACE applies to antigens from either the extracellular environment (cross-presentation) or antigens produced endogenously. Consistent with its role in MHC class I antigen processing, ACE localizes to the endoplasmic reticulum. ACE overexpression does not appear to change the overall supply of peptides available to MHC class I molecules. The immunization of wild type mice previously given ACE 10/10 macrophages enhances the efficiency of antigen-specific CD8⁺ T cell priming. These data reveal that ACE is a dynamic participant in fashioning the peptide repertoire for MHC class I molecules by modifying the C termini of peptide precursors. Manipulation of peptidase expression by antigen-presenting cells may ultimately prove a useful strategy to enhance the immune response.

Received for publication, November 26, 2007 , and in revised form, January 11, 2008.

^* This work was supported by National Institutes of Health Grants R01 DK039777 and R01 DK051445 (to K. E. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported by grants from the Fondation pour la Recherche Medicale (FRM) and Fondation Bettencourt.

² To whom correspondence should be addressed: Dept. of Pathology, Rm. 7107A WMB, 101 Woodruff Circle, Emory University, Atlanta, GA 30322. Tel.: 404-727-3134; Fax: 404-712-9625; E-mail: kbernst{at}emory.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?