CD94 Is Essential for NK Cell-Mediated Resistance to a Lethal Viral Disease

It is well established that natural killer (NK) cells confer resistance to many viral diseases, but in only a few instances the molecular mechanisms whereby NK cells recognize virus-infected cells are known. Here we show that CD94, a molecule preferentially expressed by NK cells, is essential for th...

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Published in:	Immunity (Cambridge, Mass.) Vol. 34; no. 4; pp. 579 - 589
Main Authors:	Fang, Min, Orr, Mark T., Spee, Pieter, Egebjerg, Thomas, Lanier, Lewis L., Sigal, Luis J.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 22-04-2011 Elsevier Limited
Subjects:	Animals Cell Line Cell Movement Cytomegalovirus Disease Ectromelia virus Ectromelia, Infectious - immunology Experiments Flow cytometry Humans Immune system Infections Killer Cells, Natural - immunology Laboratory animals Ligands Lymph Nodes - cytology Lymph Nodes - immunology Mice NK Cell Lectin-Like Receptor Subfamily D - immunology Orthopoxvirus Proteins Software Statistical analysis Viral infections
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Summary:	It is well established that natural killer (NK) cells confer resistance to many viral diseases, but in only a few instances the molecular mechanisms whereby NK cells recognize virus-infected cells are known. Here we show that CD94, a molecule preferentially expressed by NK cells, is essential for the resistance of C57BL/6 mice to mousepox, a disease caused by the Orthopoxvirus ectromelia virus. Ectromelia virus-infected cells expressing the major histocompatibility complex (MHC) class Ib molecule Qa-1 b are specifically recognized by the activating receptor formed by CD94 and NKG2E. Because CD94-NKG2 receptors and their ligands are highly conserved in rodents and humans, a similar mechanism may exist during human infections with the smallpox and monkeypox viruses, which are highly homologous to ectromelia virus. [Display omitted] ► Deficiency in CD94 results in susceptibility to lethal mousepox ► NK cells require CD94 to protect from mousepox ► CD94-NKG2E recognizes ECTV-infected cells in a Qa-1 b-dependent manner
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 L.J.S. and L.L.L. are both senior authors L.J.S. and L.L.L. conceived the initial idea; M.F. performed most of the experiments; L.J.S. supervised the project; M.O. generated some of the reporter cells; P.S. and T.E. produced the CD94 blocking mAb; L.J.S and L.L.L., contributed reagents and analytic tools; M.F., M.O., L.L.L., and L.J.S. discussed the general design and the analysis of experiments; M.F. and L.J.S. designed most of the experiments; L.J.S. wrote the manuscript with M.F. collaboration; M.F. and L.J.S. prepared the figures. L.J.S. and L.L.L. should be considered senior authors. All the authors approved the final manuscript. Author contributions
ISSN:	1074-7613 1097-4180
DOI:	10.1016/j.immuni.2011.02.015