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*Substance via MeSH
The Journal of Immunology, 2002, 169: 239-247.
Copyright © 2002 by The American Association of Immunologists

Genetic Control of Human NK Cell Repertoire1

Heather G. Shilling*, Neil Young2,*, Lisbeth A. Guethlein*, Nathalie W. Cheng*, Clair M. Gardiner3,*, Dolly Tyan{dagger} and Peter Parham4,*

* Departments of Structural Biology, and Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305; and {dagger} Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048

Through differential killer cell Ig-like receptor (KIR) and CD94:NKG2 gene expression, human NK cells generate diverse repertoires, each cell having an inhibitory receptor for autologous HLA class I. Using a new method for measuring repertoire difference that integrates multiple flow cytometry parameters, we found individual repertoire stability, but population variability. Correlating repertoire differences with KIR and HLA genotype for 85 sibling pairs reveals the dominant influence of KIR genotype; HLA genotype having a subtle, modulating effect on relative KIR expression frequencies. HLA and/or KIR genotype also influences CD94:NKG2A expression. After HLA-matched stem cell transplantation, KIR repertoires either recapitulated that of the donor or were generally depressed for KIR expression. Human NK cell repertoires are defined by combinations of variable KIR and HLA class I genes and conserved CD94:NKG2 genes.




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