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Modulation of Natural Killer Cell Cytotoxicity in Human Cytomegalovirus Infection: The Role of Endogenous Class I Major Histocompatibility Complex and a Viral Class I Homolog

Leong, Clement C. and Chapman, Tara L. and Bjorkman, Pamela J. and Formankova, Danuska and Mocarski, Edward S. and Phillips, Joseph H. and Lanier, Lewis L. (1998) Modulation of Natural Killer Cell Cytotoxicity in Human Cytomegalovirus Infection: The Role of Endogenous Class I Major Histocompatibility Complex and a Viral Class I Homolog. Journal of Experimental Medicine, 187 (10). pp. 1681-1687. ISSN 0022-1007. http://resolver.caltech.edu/CaltechAUTHORS:20120118-133321708

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Abstract

Natural killer (NK) cells have been implicated in early immune responses against certain viruses, including cytomegalovirus (CMV). CMV causes downregulation of class I major histocompatibility complex (MHC) expression in infected cells; however, it has been proposed that a class I MHC homolog encoded by CMV, UL18, may act as a surrogate ligand to prevent NK cell lysis of CMV-infected cells. In this study, we examined the role of UL18 in NK cell recognition and lysis using fibroblasts infected with either wild-type or UL18 knockout CMV virus, and by using cell lines transfected with the UL18 gene. In both systems, the expression of UL18 resulted in the enhanced killing of target cells. We also show that the enhanced killing is due to both UL18-dependent and -independent mechanisms, and that the killer cell inhibitory receptors (KIRs) and CD94/NKG2A inhibitory receptors for MHC class I do not play a role in affecting susceptibility of CMV-infected fibroblasts to NK cell–mediated cytotoxicity.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1084/jem.187.10.1681DOIUNSPECIFIED
http://jem.rupress.org/content/187/10/1681PublisherUNSPECIFIED
Additional Information:© 1998 Rockefeller University Press. Received for publication 3 December 1997 and in revised form 26 February 1998. We thank the members of the DNAX FACS facility for flow cytometry, and Dr. Lenore Pereira, Debra Liggett, Sasha Lazetic, and Brian Corliss for advice and reagents. DNAX Research Institute is supported by the Schering Plough Corporation. T.L Chapman is supported by a National Defense Science and Engineering Pre-Doctoral Fellowship.
Errata:The authors regret that two sentences citing the data in reference 10 were incorrectly worded. The sentences appear on p. 1681, lines 17–20 of the right column, and p. 1685, lines 35–37 of the left column. The corrected versions follow. [p. 1681] In support of this hypothesis, Farrell et al. (10) have shown that mouse CMV lacking the m144 gene is less virulent in vivo. [p. 1685] This scenario could potentially explain the decreased virulence of mouse CMV virus lacking m144 (10).
Funders:
Funding AgencyGrant Number
Schering Plough CorporationUNSPECIFIED
National Defense Science and Engineering Pre-Doctoral FellowshipUNSPECIFIED
Subject Keywords:cytomegalovirus; class I major histocompatibility complex; UL18; natural killer cell; cytotoxicity
Record Number:CaltechAUTHORS:20120118-133321708
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120118-133321708
Official Citation:Modulation of Natural Killer Cell Cytotoxicity in Human Cytomegalovirus Infection: The Role of Endogenous Class I Major Histocompatibility Complex and a Viral Class I Homolog Clement C. Leong, Tara L. Chapman, Pamela J. Bjorkman, Danuska Formankova, Edward S. Mocarski, Joseph H. Phillips, and Lewis L. Lanier J Exp Med 1998 187:1681-1687. Published May 18, 1998, doi:10.1084/jem.187.10.1681
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:28834
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:18 Jan 2012 22:46
Last Modified:26 Dec 2012 14:42

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