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 Nussbaum, A. K. Articles by Whitton, J. L. Search for Related Content PubMed PubMed Citation Articles by Nussbaum, A. K. Articles by Whitton, J. L.

Immunoproteasome-Deficient Mice Mount Largely Normal CD8⁺ T Cell Responses to Lymphocytic Choriomeningitis Virus Infection and DNA Vaccination¹

Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037

During viral infection, constitutive proteasomes are largely replaced by immunoproteasomes, which display distinct cleavage specificities, resulting in different populations of potential CD8⁺ T cell epitope peptides. Immunoproteasomes are believed to be important for the generation of many viral CD8⁺ T cell epitopes and have been implicated in shaping the immunodominance hierarchies of CD8⁺ T cell responses to influenza virus infection. However, it remains unclear whether these conclusions are generally applicable. In this study we investigated the CD8⁺ T cell responses to lymphocytic choriomeningitis virus infection and DNA immunization in wild-type mice and in mice lacking the immunoproteasome subunits LMP2 or LMP7. Although the total number of virus-specific cells was lower in LMP2 knockout mice, consistent with their having lower numbers of naive cells before infection, the kinetics of virus clearance were similar in all three mouse strains, and LMP-deficient mice mounted strong primary and secondary lymphocytic choriomeningitis virus-specific CD8⁺ T cell responses. Furthermore, the immunodominance hierarchy of the four investigated epitopes (nuclear protein 396 (NP₃₉₆) > gp33 > gp276 > NP₂₀₅) was well maintained. We observed a slight reduction in the NP₂₀₅-specific response in LMP2-deficient mice, but this had no demonstrable biological consequence. DNA vaccination of LMP2- and LMP7-deficient mice induced CD8⁺ T cell responses that were slightly lower than, although not significantly different from, those induced in wild-type mice. Taken together, our results challenge the notion that immunoproteasomes are generally needed for effective antiviral CD8⁺ T cell responses and for the shaping of immunodominance hierarchies. We conclude that the immunoproteasome may affect T cell responses to only a limited number of viral epitopes, and we propose that its main biological function may lie elsewhere.

This article has been cited by other articles:

				N. J. Steers, K. K. Peachman, S. R. McClain, C. R. Alving, and M. Rao Human Immunodeficiency Virus Type 1 Gag p24 Alters the Composition of Immunoproteasomes and Affects Antigen Presentation J. Virol., July 15, 2009; 83(14): 7049 - 7061. [Abstract] [Full Text] [PDF]

				M. D. Robek, M. L. Garcia, B. S. Boyd, and F. V. Chisari Role of Immunoproteasome Catalytic Subunits in the Immune Response to Hepatitis B Virus J. Virol., January 15, 2007; 81(2): 483 - 491. [Abstract] [Full Text] [PDF]

				K. C. Pang, M. T. Sanders, J. J. Monaco, P. C. Doherty, S. J. Turner, and W. Chen Immunoproteasome Subunit Deficiencies Impact Differentially on Two Immunodominant Influenza Virus-Specific CD8+ T Cell Responses J. Immunol., December 1, 2006; 177(11): 7680 - 7688. [Abstract] [Full Text] [PDF]

				B. Strehl, T. Joeris, M. Rieger, A. Visekruna, K. Textoris-Taube, S. H. E. Kaufmann, P.-M. Kloetzel, U. Kuckelkorn, and U. Steinhoff Immunoproteasomes Are Essential for Clearance of Listeria monocytogenes in Nonlymphoid Tissues but Not for Induction of Bacteria-Specific CD8+ T Cells J. Immunol., November 1, 2006; 177(9): 6238 - 6244. [Abstract] [Full Text] [PDF]

				D. Masopust, S.-J. Ha, V. Vezys, and R. Ahmed Stimulation History Dictates Memory CD8 T Cell Phenotype: Implications for Prime-Boost Vaccination J. Immunol., July 15, 2006; 177(2): 831 - 839. [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]

				P. Osterloh, K. Linkemann, S. Tenzer, H.-G. Rammensee, M. P. Radsak, D. H. Busch, and H. Schild Proteasomes shape the repertoire of T cells participating in antigen-specific immune responses PNAS, March 28, 2006; 103(13): 5042 - 5047. [Abstract] [Full Text] [PDF]