title: Development and function of CD94-deficient natural killer cells.
abstract: The CD94 transmembrane-anchored glycoprotein forms disulfide-bonded heterodimers with the NKG2A subunit to form an inhibitory receptor or with the NKG2C or NKG2E subunits to assemble a receptor complex with activating DAP12 signaling proteins. CD94 receptors expressed on human and mouse NK cells and T cells have been proposed to be important in NK cell tolerance to self, play an important role in NK cell development, and contribute to NK cell-mediated immunity to certain infections including human cytomegalovirus. We generated a gene-targeted CD94-deficient mouse to understand the role of CD94 receptors in NK cell biology. CD94-deficient NK cells develop normally and efficiently kill NK cell-susceptible targets. Lack of these CD94 receptors does not alter control of mouse cytomegalovirus, lymphocytic choriomeningitis virus, vaccinia virus, or Listeria monocytogenes. Thus, the expression of CD94 and its associated NKG2A, NKG2C, and NKG2E subunits is dispensable for NK cell development, education, and many NK cell functions.
authors.affiliation: Department of Microbiology and Immunology and the Cancer Research Institute, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Orr
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Sigal
authors.forename: Pieter
authors.initials: P
authors.lastname: Spee
authors.forename: Thomas
authors.initials: T
authors.lastname: Egebjerg
authors.forename: Erik
authors.initials: E
authors.lastname: Dissen
authors.forename: Sigbjørn
authors.initials: S
authors.lastname: Fossum
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Phillips
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D003587:Cytomegalovirus / Q000235:genetics*; D019281:Dimerization; D005786:Gene Expression Regulation; D006801:Humans; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism; D008089:Listeria monocytogenes / Q000378:metabolism; D008088:Listeriosis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics / Q000378:metabolism; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D014615:Vaccinia / Q000378:metabolism
chemical_list: C497869:KLRD1 protein, human; C527057:Klrc1 protein, mouse; C527060:Klrc2 protein, mouse; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D