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Novel APC-like properties of human NK cells directly regulate T cell activation

Jacob Hanna, Ofer Mandelboim
doi: https://doi.org/10.1101/016816
Jacob Hanna
1The Lautenberg Center for General and Tumor Immunology, Hebrew University–Hadassah Medical School, Jerusalem, Israel
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Ofer Mandelboim
1The Lautenberg Center for General and Tumor Immunology, Hebrew University–Hadassah Medical School, Jerusalem, Israel
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Abstract

Initiation of the adaptive immune response is dependent on the priming of naive T cells by APCs. Proteomic analysis of unactivated and activated human NK cell membrane–enriched fractions demonstrated that activated NK cells can efficiently stimulate T cells, since they upregulate MHC class II molecules and multiple ligands for TCR costimulatory molecules. Furthermore, by manipulating antigen administration, we show that NK cells possess multiple independent unique pathways for antigen uptake. These results highlight NK cell–mediated cytotoxicity and specific ligand recognition by cell surface–activating receptors on NK cells as unique mechanisms for antigen capturing and presentation. In addition, we analyzed the T cell–activating potential of human NK cells derived from different clinical conditions, such as inflamed tonsils and noninfected and CMV–infected uterine decidual samples, and from transporter-associated processing antigen 2–deficient patients. This in vivo analysis revealed that proinflammatory, but not immune-suppressive, microenvironmental requirements can selectively dictate upregulation of T cell–activating molecules on NK cells. Taken together, these observations offer new and unexpected insights into the direct interactions between NK and T cells and suggest novel APC-like activating functions for human NK cells.

ANK
activated NK
dNK
decidual NK
HA
hemagglutinin
ImDC
immature DC
MDC
mature DC
MFI
mean fluorescence intensity
NCR
natural cytotoxicity receptor
TAP2
transporter-associated processing antigen 2
UaNK
unactivated NK
Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted March 30, 2015.
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Novel APC-like properties of human NK cells directly regulate T cell activation
Jacob Hanna, Ofer Mandelboim
bioRxiv 016816; doi: https://doi.org/10.1101/016816
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Novel APC-like properties of human NK cells directly regulate T cell activation
Jacob Hanna, Ofer Mandelboim
bioRxiv 016816; doi: https://doi.org/10.1101/016816

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