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 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 Towne, C. F. Articles by Rock, K. L. Search for Related Content PubMed PubMed Citation Articles by Towne, C. F. Articles by Rock, K. L. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Substance via MeSH

Leucine Aminopeptidase Is Not Essential for Trimming Peptides in the Cytosol or Generating Epitopes for MHC Class I Antigen Presentation¹

Charles F. Towne^*, Ian A. York^*, Joost Neijssen, Margaret L. Karow, Andrew J. Murphy, David M. Valenzuela, George D. Yancopoulos, Jacques J. Neefjes and Kenneth L. Rock^2,*

^* Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655; Division of Tumor Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; and Regeneron Pharmaceuticals, Tarrytown, NY 10591

To detect viral infections and tumors, CD8⁺ T lymphocytes monitor cells for the presence of antigenic peptides bound to MHC class I molecules. The majority of MHC class I-presented peptides are generated from the cleavage of cellular and viral proteins by the ubiquitin-proteasome pathway. Many of the oligopeptides produced by this process are too long to stably bind to MHC class I molecules and require further trimming for presentation. Leucine aminopeptidase (LAP) is an IFN-inducible cytosolic aminopeptidase that can trim precursor peptides to mature epitopes and has been thought to play an important role in Ag presentation. To examine the role of LAP in generating MHC class I peptides in vivo, we generated LAP-deficient mice and LAP-deficient cell lines. These mutant mice and cells are viable and grow normally. The trimming of peptides in LAP-deficient cells is not reduced under basal conditions or after stimulation with IFN. Similarly, there is no reduction in presentation of peptides from precursor or full-length Ag constructs or in the overall supply of peptides from cellular proteins to MHC class I molecules even after stimulation with IFN. After viral infection, LAP-deficient mice generate normal CTL responses to seven epitopes from three different viruses. These data demonstrate that LAP is not an essential enzyme for generating most MHC class I-presented peptides and reveal redundancy in the function of cellular aminopeptidases.

This article has been cited by other articles:

				E. Kim, H. Kwak, and K. Ahn Cytosolic Aminopeptidases Influence MHC Class I-Mediated Antigen Presentation in an Allele-Dependent Manner J. Immunol., December 1, 2009; 183(11): 7379 - 7387. [Abstract] [Full Text] [PDF]

				M. Kawahara, I. A. York, A. Hearn, D. Farfan, and K. L. Rock Analysis of the Role of Tripeptidyl Peptidase II in MHC Class I Antigen Presentation In Vivo J. Immunol., November 15, 2009; 183(10): 6069 - 6077. [Abstract] [Full Text] [PDF]

				C. F. Towne, I. A. York, J. Neijssen, M. L. Karow, A. J. Murphy, D. M. Valenzuela, G. D. Yancopoulos, J. J. Neefjes, and K. L. Rock Puromycin-Sensitive Aminopeptidase Limits MHC Class I Presentation in Dendritic Cells but Does Not Affect CD8 T Cell Responses during Viral Infections J. Immunol., February 1, 2008; 180(3): 1704 - 1712. [Abstract] [Full Text] [PDF]

				E. Firat, J. Huai, L. Saveanu, S. Gaedicke, P. Aichele, K. Eichmann, P. van Endert, and G. Niedermann Analysis of Direct and Cross-Presentation of Antigens in TPPII Knockout Mice1 J. Immunol., December 15, 2007; 179(12): 8137 - 8145. [Abstract] [Full Text] [PDF]

				C. F. Towne, I. A. York, L. B. Watkin, J. S. Lazo, and K. L. Rock Analysis of the Role of Bleomycin Hydrolase in Antigen Presentation and the Generation of CD8 T Cell Responses J. Immunol., June 1, 2007; 178(11): 6923 - 6930. [Abstract] [Full Text] [PDF]

				M. L. Altrich-VanLith, M. Ostankovitch, J. M. Polefrone, C. A. Mosse, J. Shabanowitz, D. F. Hunt, and V. H. Engelhard Processing of a Class I-Restricted Epitope from Tyrosinase Requires Peptide N-Glycanase and the Cooperative Action of Endoplasmic Reticulum Aminopeptidase 1 and Cytosolic Proteases J. Immunol., October 15, 2006; 177(8): 5440 - 5450. [Abstract] [Full Text] [PDF]

				I. A. York, N. Bhutani, S. Zendzian, A. L. Goldberg, and K. L. Rock Tripeptidyl Peptidase II Is the Major Peptidase Needed to Trim Long Antigenic Precursors, but Is Not Required for Most MHC Class I Antigen Presentation J. Immunol., August 1, 2006; 177(3): 1434 - 1443. [Abstract] [Full Text] [PDF]

				I. A. York, M. A. Brehm, S. Zendzian, C. F. Towne, and K. L. Rock Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance PNAS, June 13, 2006; 103(24): 9202 - 9207. [Abstract] [Full Text] [PDF]