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Orderly and nonstochastic acquisition of CD94/NKG2 receptors by developing NK cells derived from embryonic stem cells in vitro.
J Immunol. 2002 May 15; 168(10):4980-7.JI

Abstract

In mice there are two families of MHC class I-specific receptors, namely the Ly49 and CD94/NKG2 receptors. The latter receptors recognize the nonclassical MHC class I Qa-1(b) and are thought to be responsible for the recognition of missing-self and the maintenance of self-tolerance of fetal and neonatal NK cells that do not express Ly49. Currently, how NK cells acquire individual CD94/NKG2 receptors during their development is not known. In this study, we have established a multistep culture method to induce differentiation of embryonic stem (ES) cells into the NK cell lineage and examined the acquisition of CD94/NKG2 by NK cells as they differentiate from ES cells in vitro. ES-derived NK (ES-NK) cells express NK cell-associated proteins and they kill certain tumor cell lines as well as MHC class I-deficient lymphoblasts. They express CD94/NKG2 heterodimers, but not Ly49 molecules, and their cytotoxicity is inhibited by Qa-1(b) on target cells. Using RT-PCR analysis, we also report that the acquisition of these individual receptor gene expressions during different stages of differentiation from ES cells to NK cells follows a predetermined order, with their order of acquisition being first CD94; subsequently NKG2D, NKG2A, and NKG2E; and finally, NKG2C. Single-cell RT-PCR showed coexpression of CD94 and NKG2 genes in most ES-NK cells, and flow cytometric analysis also detected CD94/NKG2 on most ES-NK cells, suggesting that the acquisition of these receptors by ES-NK cells in vitro is nonstochastic, orderly, and cumulative.

Authors+Show Affiliations

Terry Fox Laboratory, British Columbia Cancer Agency, University of British Columbia, 601 West 10th Avenue, Vancouver, British Columbia, Canada V5Z 1L3.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11994449

Citation

Lian, Rebecca H., et al. "Orderly and Nonstochastic Acquisition of CD94/NKG2 Receptors By Developing NK Cells Derived From Embryonic Stem Cells in Vitro." Journal of Immunology (Baltimore, Md. : 1950), vol. 168, no. 10, 2002, pp. 4980-7.
Lian RH, Maeda M, Lohwasser S, et al. Orderly and nonstochastic acquisition of CD94/NKG2 receptors by developing NK cells derived from embryonic stem cells in vitro. J Immunol. 2002;168(10):4980-7.
Lian, R. H., Maeda, M., Lohwasser, S., Delcommenne, M., Nakano, T., Vance, R. E., Raulet, D. H., & Takei, F. (2002). Orderly and nonstochastic acquisition of CD94/NKG2 receptors by developing NK cells derived from embryonic stem cells in vitro. Journal of Immunology (Baltimore, Md. : 1950), 168(10), 4980-7.
Lian RH, et al. Orderly and Nonstochastic Acquisition of CD94/NKG2 Receptors By Developing NK Cells Derived From Embryonic Stem Cells in Vitro. J Immunol. 2002 May 15;168(10):4980-7. PubMed PMID: 11994449.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Orderly and nonstochastic acquisition of CD94/NKG2 receptors by developing NK cells derived from embryonic stem cells in vitro. AU - Lian,Rebecca H, AU - Maeda,Motoi, AU - Lohwasser,Stefan, AU - Delcommenne,Marc, AU - Nakano,Toru, AU - Vance,Russell E, AU - Raulet,David H, AU - Takei,Fumio, PY - 2002/5/8/pubmed PY - 2002/6/20/medline PY - 2002/5/8/entrez SP - 4980 EP - 7 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 168 IS - 10 N2 - In mice there are two families of MHC class I-specific receptors, namely the Ly49 and CD94/NKG2 receptors. The latter receptors recognize the nonclassical MHC class I Qa-1(b) and are thought to be responsible for the recognition of missing-self and the maintenance of self-tolerance of fetal and neonatal NK cells that do not express Ly49. Currently, how NK cells acquire individual CD94/NKG2 receptors during their development is not known. In this study, we have established a multistep culture method to induce differentiation of embryonic stem (ES) cells into the NK cell lineage and examined the acquisition of CD94/NKG2 by NK cells as they differentiate from ES cells in vitro. ES-derived NK (ES-NK) cells express NK cell-associated proteins and they kill certain tumor cell lines as well as MHC class I-deficient lymphoblasts. They express CD94/NKG2 heterodimers, but not Ly49 molecules, and their cytotoxicity is inhibited by Qa-1(b) on target cells. Using RT-PCR analysis, we also report that the acquisition of these individual receptor gene expressions during different stages of differentiation from ES cells to NK cells follows a predetermined order, with their order of acquisition being first CD94; subsequently NKG2D, NKG2A, and NKG2E; and finally, NKG2C. Single-cell RT-PCR showed coexpression of CD94 and NKG2 genes in most ES-NK cells, and flow cytometric analysis also detected CD94/NKG2 on most ES-NK cells, suggesting that the acquisition of these receptors by ES-NK cells in vitro is nonstochastic, orderly, and cumulative. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/11994449/Orderly_and_nonstochastic_acquisition_of_CD94/NKG2_receptors_by_developing_NK_cells_derived_from_embryonic_stem_cells_in_vitro_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=11994449 DB - PRIME DP - Unbound Medicine ER -