Strain-dependent expression of four structurally related rat Ly49 receptors; correlation with NK gene complex haplotype and NK alloreactivity |
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Authors: | Lise Kveberg Ke-Zheng Dai Erik Dissen James C Ryan Bent Rolstad John T Vaage Christian Naper |
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Institution: | (1) Institute of Immunology (IMMI), Rikshospitalet-Radiumhospitalet Medical Centre, University of Oslo, 0027 Oslo, Norway;(2) Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway;(3) Veterans Affairs Medical Center, University of California-San Francisco, San Francisco, CA 94121, USA |
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Abstract: | Natural killer (NK) cells from certain rat strains promptly kill MHC allogeneic lymphocytes in vivo, a rejection phenomenon termed allogeneic lymphocyte cytotoxicity (ALC). ALC can be reproduced in vitro, and is preferentially mediated by a subset of NK cells expressing the Ly49 stimulatory receptor 3 (Ly49s3) in PVG strain
rats. Functional studies have suggested that Ly49s3 triggers NK cell alloreactivity, but its importance relative to other
Ly49 receptors has not been investigated. In this study, we have characterized three rat Ly49 receptors with close sequence
similarity to Ly49s3 in the extracellular region, i.e., Ly49s4, Ly49 inhibitory receptor 3 (Ly49i3), and Ly49i4. Similar to
Ly49s3, Ly49s4 mediated cellular activation while Ly49i4 inhibited NK cytolytic function. Ly49s4, -i3, and -i4 all reacted
with a previously described anti-Ly49s3 monoclonal antibody (mAb) (DAR13), but not a novel mAb (STOK6), which was shown to
be specific for Ly49s3. Expression of these Ly49 receptors varied markedly between inbred strains, in patterns related to
their NK gene complex (NKC) haplotype, and ability to mediate ALC. Three major groups of NKC haplotypes could be discerned
by restriction fragment length polymorphism analysis. Ly49s3 was present in strains from one of the groups, which corresponded
with the “high” ALC responders. Ly49s3 surface expression was also markedly reduced in the presence of its putative MHC class
Ib ligand(s) in MHC congenic strains. These data support the notion that Ly49s3 functions as a triggering MHC receptor both
in vitro and in vivo. MHC ligands for the other three Ly49 receptors remain to be determined. |
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Keywords: | Natural Killer cells MHC Ly49 receptors Alloreactivity Rodent |
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