Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 38, Issue 12, Pages 3474-3486Publisher
WILEY
DOI: 10.1002/eji.200838407
Keywords
HLA class I molecules; Killer cell immunoglobulin-like receptors; NK cells; NK repertoire
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Funding
- Ligue Nationale contre le Cancer
- Etablissement Francais du Sang [21/2006]
- Agence de la Biomedecine
- NAGMO association
- Comite departemental de Loire-Atlantique de la Ligue contre le Cancer
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NK-cell function is regulated by a balance between inhibitory and activating killer cell immunoglobulin-like receptors (KIR) that specifically recognize HLA class I molecules. Using KIR-specific mAb to discriminate between KIR2DS1 and KIR2DL1 receptors, we show that KIR2DS1(+) NK cells are C2-alloreactive only from C2(-) individuals. Moreover, using an in vitro model of NK-cell expansion, we show here that the frequency of KIR2DL1(+) NK cells is significantly higher in the absence of C2 ligand on stimulator EBV-B cells than in its presence. This observation was made regardless of the presence or absence of the autologous C2 ligand, suggesting that the C2- EBV-B stimulator cells used in this in vitro model could activate unlicensed KIR2DL1(+) NK cells. In the case of KIR2DL1(+)/S1(+) genotyped individuals, KIR2DS1(+) NK-cell frequency was increased after stimulation with C2(+) compared with C2(-) stimulator B cells, but only from C2(-) individuals. Altogether, these data highlight the C2 alloreactivity of KIR2DS1(+) NK cells that is only observed in C2(-) individuals. These results provide new insights into the way in which NK KIR cell expansion might be regulated in an allogeneic environment.
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