title: HLA-C levels impact natural killer cell subset distribution and function.
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 CD56negNKs 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.
authors: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors: Magdalena
authors: M
authors: Sips
authors: Department of Endocrinology, Tangdu Hospital, Fourth Military Medical University, Xi'an, ShaanXi, China.
authors: Qingquan
authors: Q
authors: Liu
authors: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
authors: Monia
authors: M
authors: Draghi
authors: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
authors: Musie
authors: M
authors: Ghebremichael
authors: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; University Hospital Basel, Basel, Switzerland.
authors: Christoph T
authors: CT
authors: Berger
authors: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
authors: Todd J
authors: TJ
authors: Suscovich
authors: Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, ShaanXi, China.
authors: Yongtao
authors: Y
authors: Sun
authors: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
authors: Bruce D
authors: BD
authors: Walker
authors: 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.
authors: Mary
authors: M
authors: Carrington
authors: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors: Marcus
authors: M
authors: Altfeld
authors: Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.
authors: Peter
authors: P
authors: Brouckaert
authors: 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.
authors: Philip L
authors: PL
authors: De Jager
authors: Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. Electronic address: galter@mgh.harvard.edu.
authors: Galit
authors: G
authors: Alter
mesh_terms: D000293:Adolescent; D000328:Adult; D058070:Asymptomatic Diseases; D015331:Cohort Studies; D003602:Cytotoxicity, Immunologic; D005260:Female; D005787:Gene Frequency; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D015236:HLA-C Antigens / Q000235:genetics / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics / Q000378:metabolism; D019562:Viral Load; D055815:Young Adult
chemical_list: D015236:HLA-C Antigens; D054340:Receptors, KIR; D007371:Interferon-gamma
keywords: HIV-1; HLA-C; KIR; Natural killer cells