Education of human natural killer cells by activating killer cell immunoglobulin-like receptors.

Abstract:

:Expression of inhibitory killer cell immunoglobulin-like receptors (KIRs) specific for self-major histocompatibility complex (MHC) class I molecules provides an educational signal that generates functional natural killer (NK) cells. However, the effects of activating KIRs specific for self-MHC class I on NK-cell education remain elusive. Here, we provide evidence that the activating receptor KIR2DS1 tunes down the responsiveness of freshly isolated human NK cells to target cell stimulation in donors homozygous for human leukocyte antigen (HLA)-C2, the ligand of KIR2DS1. The tuning was apparent in KIR2DS1(+) NK cells lacking expression of inhibitory KIRs and CD94/NKG2A, as well as in KIR2DS1(+) NK cells coexpressing the inhibitory MHC class I-specific receptors CD94/NKG2A and KIR2DL3, but not KIR2DL1. However, the tuning of responsiveness was restricted to target cell recognition because KIR2DS1(+) NK cells responded well to stimulation with exogenous cytokines. Our results provide the first example of human NK-cell education by an activating KIR and suggest that the education of NK cells via activating KIRs is a mechanism to secure tolerance that complements education via inhibitory KIRs.

journal_name

Blood

journal_title

Blood

authors

Fauriat C,Ivarsson MA,Ljunggren HG,Malmberg KJ,Michaëlsson J

doi

10.1182/blood-2009-09-245746

subject

Has Abstract

pub_date

2010-02-11 00:00:00

pages

1166-74

issue

6

eissn

0006-4971

issn

1528-0020

pii

blood-2009-09-245746

journal_volume

115

pub_type

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