The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
A correction to this article has been published: J. Exp. Med. 188 (3) 615
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 141K)
Right arrow PPT slides of all figures
Right arrow Correction (v188,p615)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Leong, C. C.
Right arrow Articles by Lanier, L. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Leong, C. C.
Right arrow Articles by Lanier, L. L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1998/5/1681/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 10, May 18, 1998 1681-1687

Articles

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{ddagger}, Pamela J. Bjorkman{ddagger}, Danuska Formankova§, Edward S. Mocarski§, Joseph H. Phillips*, and Lewis L. Lanier*

From the * Department of Immunobiology, DNAX Institute of Molecular and Cell Biology, Palo Alto, California 94304; the {ddagger} Division of Biology 156-29 and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125; and the § Department of Microbiology and Immunology, Stanford University, Stanford, California 94305

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.

Key Words: cytomegalovirus • class I major histocompatibility complex • UL18 • natural killer cell • cytotoxicity

Address correspondence to Clement Leong, DNAX Research Institute, 901 California Ave., Palo Alto, CA 94304. Phone: 650-496-1241; Fax: 650-496-1200; E-mail: leong{at}dnax.org

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.

Abbreviations used: β2M, β2-microglobulin; CHO, Chinese hamster ovary; cIg, control Ig; hCMV, human cytomegalovirus; HFF, human foreskin fibroblasts; ICAM-1, intracellular adhesion molecule 1; KIR, killer cell inhibitory receptor; MOI, multiplicity of infection.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS