NDLI: HLA reduces killer cell Ig-like receptor expression level and frequency in a humanized mouse model.

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HLA reduces killer cell Ig-like receptor expression level and frequency in a humanized mouse model.

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HLA reduces killer cell Ig-like receptor expression level and frequency in a humanized mouse model.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Retière, Christelle Salvatori, Daniela Trowsdale, John Van Bergen, Jeroen Raulet, David H. Koning, Frits Van Pel, Melissa Thompson, Allan
Description	Country affiliation: Netherlands Author Affiliation: van Bergen J ( Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands. J.van_Bergen@lumc.nl)
Abstract	NK cells use NK cell receptors to be able to recognize and eliminate infected, transformed, and allogeneic cells. Human NK cells are prevented from killing autologous healthy cells by virtue of inhibitory NKRs, primarily killer cell Ig-like receptors (KIR) that bind 'self' HLA class I molecules. Individual NK cells stably express a selected set of KIR, but it is currently disputed whether the fraction of NK cells expressing a particular inhibitory KIR is influenced by the presence of the corresponding HLA ligand. The extreme polymorphism of the KIR and HLA loci, with wide-ranging affinities for individual KIR and HLA allele combinations, has made this issue particularly hard to tackle. In this study, we used a transgenic mouse model to investigate the effect of HLA on KIR repertoire and function in the absence of genetic variation inside and outside the KIR locus. These H-2K(b-/-) and H-2D(b-/-) mice lacked ligands for inhibitory Ly49 receptors and were transgenic for HLA-Cw3 and a KIR B haplotype. In this reductionist system, the presence of HLA-Cw3 reduced the frequency of KIR2DL2(+) cells, as well as the surface expression levels of KIR2DL2. In addition, in the presence of HLA-Cw3, the frequency of NKG2A(+) cells and the surface expression levels of NKG2A were reduced. In line with these findings, both transgene-encoded KIR and endogenous NKG2A contributed to the rejection of cells lacking HLA-Cw3. These findings support the idea that HLA influences the human KIR repertoire.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1200650
Journal	The Journal of Immunology
Issue Number	6
Volume Number	190
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-03-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Hla-c Antigens Physiology Models, Immunological Receptors, Kir2dl2 Antagonists & Inhibitors Receptors, Kir Animals H-2 Antigens Genetics Metabolism Killer Cells, Natural Immunology Pathology Lymphocyte Depletion Mice Mice, Inbred C57bl Mice, Inbred Cba Mice, Knockout Mice, Transgenic Nk Cell Lectin-like Receptor Subfamily C Biosynthesis Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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