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 Shen, X. Articles by Siliciano, R. F. Search for Related Content PubMed PubMed Citation Articles by Shen, X. Articles by Siliciano, R. F.

Direct Priming and Cross-Priming Contribute Differentially to the Induction of CD8⁺ CTL Following Exposure to Vaccinia Virus Via Different Routes¹

Xuefei Shen^*, S. B. Justin Wong, Christopher B. Buck, Jiangwen Zhang and Robert F. Siliciano^2,*,,

Programs in ^* Biochemistry, Cellular and Molecular Biology, and Cellular and Molecular Medicine, and Graduate Program in Immunology and Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205

To explore the relative importance of direct presentation vs cross-priming in the induction of CTL responses to viruses and viral vectors, we generated a recombinant vaccinia vector, vUS11, expressing the human CMV (HCMV) protein US11. US11 dislocates most allelic forms of human and murine MHC class I heavy chains from the lumen of the endoplasmic reticulum into the cytosol, where they are degraded by proteasomes. Expression of US11 dramatically decreased the presentation of viral Ag and CTL recognition of infected cells in vitro without significantly reducing total cell surface MHC class I levels. However, because US11 is an endoplasmic reticulum resident membrane protein, it cannot block presentation by non-infected cells that take up Ag through the cross-priming pathway. We show that the expression of US11 strongly inhibits the induction of primary CD8⁺ CTLs when the infection occurs via the i.p. or i.v. route, demonstrating that direct priming is critical for the induction of CTL responses to viral infections introduced via these routes. This effect is less dramatic following i.m. infection and is minimal after s.c. or intradermal infection. Thus, classic MHC class I Ag presentation and cross-priming contribute differentially to the induction of CD8⁺ CTLs following exposure to vaccinia virus via different routes.

This article has been cited by other articles:

				I. A. Cockburn, S. Chakravarty, M. G. Overstreet, A. Garcia-Sastre, and F. Zavala Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation J. Immunol., January 1, 2008; 180(1): 64 - 71. [Abstract] [Full Text] [PDF]

				G. Gasteiger, W. Kastenmuller, R. Ljapoci, G. Sutter, and I. Drexler Cross-Priming of Cytotoxic T Cells Dictates Antigen Requisites for Modified Vaccinia Virus Ankara Vector Vaccines J. Virol., November 1, 2007; 81(21): 11925 - 11936. [Abstract] [Full Text] [PDF]

				A. D. Bins, M. C. Wolkers, M. D. van den Boom, J. B. A. G. Haanen, and T. N. M. Schumacher In Vivo Antigen Stability Affects DNA Vaccine Immunogenicity J. Immunol., August 15, 2007; 179(4): 2126 - 2133. [Abstract] [Full Text] [PDF]

				K. Saito, T. Yajima, S. Kumabe, T. Doi, H. Yamada, S. Sad, H. Shen, and Y. Yoshikai Impaired Protection against Mycobacterium bovis Bacillus Calmette-Guerin Infection in IL-15-Deficient Mice J. Immunol., February 15, 2006; 176(4): 2496 - 2504. [Abstract] [Full Text] [PDF]

				L. N. Steele, Z. R. Balsara, and M. N. Starnbach Hematopoietic Cells Are Required to Initiate a Chlamydia trachomatis-Specific CD8+ T Cell Response J. Immunol., November 15, 2004; 173(10): 6327 - 6337. [Abstract] [Full Text] [PDF]

				S. B. J. Wong, C. B. Buck, X. Shen, and R. F. Siliciano An Evaluation of Enforced Rapid Proteasomal Degradation as a Means of Enhancing Vaccine-Induced CTL Responses J. Immunol., September 1, 2004; 173(5): 3073 - 3083. [Abstract] [Full Text] [PDF]

				A. M. Thomas, L. M. Santarsiero, E. R. Lutz, T. D. Armstrong, Y.-C. Chen, L.-Q. Huang, D. A. Laheru, M. Goggins, R. H. Hruban, and E. M. Jaffee Mesothelin-specific CD8+ T Cell Responses Provide Evidence of In Vivo Cross-Priming by Antigen-Presenting Cells in Vaccinated Pancreatic Cancer Patients J. Exp. Med., August 2, 2004; 200(3): 297 - 306. [Abstract] [Full Text] [PDF]

				S. Mercier, S. Verhaagh, J. Goudsmit, A. Lemckert, M. Monteil, M. Havenga, and M. Eloit Adenovirus fibre exchange alters cell tropism in vitro but not transgene-specific T CD8+ immune responses in vivo J. Gen. Virol., May 1, 2004; 85(5): 1227 - 1236. [Abstract] [Full Text] [PDF]

				C. Maranon, J.-F. Desoutter, G. Hoeffel, W. Cohen, D. Hanau, and A. Hosmalin Dendritic cells cross-present HIV antigens from live as well as apoptotic infected CD4+ T lymphocytes PNAS, April 20, 2004; 101(16): 6092 - 6097. [Abstract] [Full Text] [PDF]

				P. Daftarian, S. Ali, R. Sharan, S. F. Lacey, C. La Rosa, J. Longmate, C. Buck, R. F. Siliciano, and D. J. Diamond Immunization with Th-CTL Fusion Peptide and Cytosine-Phosphate-Guanine DNA in Transgenic HLA-A2 Mice Induces Recognition of HIV-Infected T Cells and Clears Vaccinia Virus Challenge J. Immunol., October 15, 2003; 171(8): 4028 - 4039. [Abstract] [Full Text] [PDF]

				R. J. Webby, S. Andreansky, J. Stambas, J. E. Rehg, R. G. Webster, P. C. Doherty, and S. J. Turner Protection and compensation in the influenza virus-specific CD8+ T cell response PNAS, June 10, 2003; 100(12): 7235 - 7240. [Abstract] [Full Text] [PDF]