|
Title
|
|
|
|
Impact of the variable killer Ig-like receptor-human leukocyte antigen interactions on natural killer cell cytotoxicity toward foreign CD4 T cells
|
|
|
Author
|
|
|
|
|
|
|
Abstract
|
|
|
|
| Background: Natural killer (NK) cells are known to mount a response against foreign target cells, where the absence of the dominant inhibitory killer Ig-like receptor (KIR)-human leukocyte antigen (HLA) interaction immensely lowers the threshold for NK cell activation. NK cells could thus constitute a vital part in the mucosal defense against cell-associated sexually transmitted diseases. Here, we performed a detailed analysis of hitherto unexplored KIR-HLA-incompatible NK cell interactions. Methods and findings: In vitro, healthy NK cells were cocultured with CD4+ T cells derived from human immunodeficiency virus-1 patients, and the KIR-specific NK cell cytotoxicity was measured using flow cytometry. Genotyping of KIR and HLA predicted the KIR-HLA interactions occurring during these 124 allogeneic encounters. KIR2DL1+ NK cells were seen as the strongest intrinsic responders in the absence of their ligand with a 3.2-fold increase in KIR2DL1+ NK cells in the total NK cell response. An association between the size of the alloreactive NK cell population and the amount of CD4+ T cell death (p = 0.0023) and NK cell degranulation (p = 0.0036) was only present in NK cell donors with an activating KIR haplotype. conclusion: We demonstrate differences in the activating effect of KIR-HLA incompatibility according to the KIR involved, with KIR2DL1 as the strongest responder. An activating KIR haplotype optimized the contribution of KIR-HLA-incompatible NK cells in the total NK cell response. |
|
|
|
Language
|
|
|
|
English
|
|
|
Source (journal)
|
|
|
|
Frontiers in immunology. - Place of publication unknown
|
|
|
Publication
|
|
|
|
Place of publication unknown
:
2018
|
|
|
ISSN
|
|
|
|
1664-3224
|
|
|
DOI
|
|
|
|
10.3389/FIMMU.2018.01588
|
|
|
Volume/pages
|
|
|
|
9
(2018)
, 11 p.
|
|
|
Article Reference
|
|
|
|
1588
|
|
|
ISI
|
|
|
|
000437882800001
|
|
|
Pubmed ID
|
|
|
|
30038628
|
|
|
Medium
|
|
|
|
E-only publicatie
|
|
|
Full text (Publisher's DOI)
|
|
|
|
|
|
|
Full text (open access)
|
|
|
|
|
|