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Hum Immunol. 2016 Dec;77(12):1147-1153. doi: 10.1016/j.humimm.2016.08.004. Epub 2016 Aug 10.

HLA-C levels impact natural killer cell subset distribution and function.

Author information

1
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
2
Department of Endocrinology, Tangdu Hospital, Fourth Military Medical University, Xi'an, ShaanXi, China.
3
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
4
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; University Hospital Basel, Basel, Switzerland.
5
Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, ShaanXi, China.
6
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
7
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
8
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
9
Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Womens Hospital, Boston, MA, USA; Harvard Medical School, Cambridge, MA, USA; Program in Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
10
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. Electronic address: galter@mgh.harvard.edu.

Abstract

Differences in HLA-C expression are inversely correlated with HIV viral load set-point and slower progression to AIDS, linked to enhanced cytotoxic T cell immunity. Yet, beyond T cells, HLA-C serves as a dominant ligand for natural killer (NK) cell killer immunoglobulin-like receptors (KIR). Thus, we speculated that HLA-C expression levels may also impact NK activity, thereby modulating HIV antiviral control. Phenotypic and functional profiling was performed on freshly isolated PBMCs. HLA-C expression was linked to changes in NK subset distribution and licensing, particularly in HLA-C1/C1, KIR2DL3+2DL2-individuals. Moreover, high levels of HLA-C, were associated with reduced frequencies of anergic CD56neg NKs and lower frequencies of KIR2DL1/2/3+ NK cells, pointing to an HLA-C induced influence on the NK cell development in the absence of disease. In HIV infection, several spontaneous controllers, that expressed higher levels of HLA-C demonstrated robust NK-IFN-γ secretion in response to target cells, highlighting a second disease induced licensing phenotype. Thus this population study points to a potential role for HLA-C levels both in NK cell education and development.

KEYWORDS:

HIV-1; HLA-C; KIR; Natural killer cells

PMID:
27521484
DOI:
10.1016/j.humimm.2016.08.004
[Indexed for MEDLINE]

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