Increased frequency and function of KIR2DL1-3⁺ NK cells in primary HIV-1 infection are determined by HLA-C group haplotypes.

Abstract

The acquisition and maintenance of NK-cell function is mediated by inhibitory killer-cell immunoglobulin-like receptors (KIRs) through their interaction with HLA class I molecules. Recently, HLA-C expression levels were shown to be correlated with protection against multiple outcomes of HIV-1 infection; however, the underlying mechanisms are poorly understood. As HLA-C is the natural ligand for the inhibitory receptors KIR2DL1 and KIR2DL2/3, we sought to determine whether HLA-C group haplotypes affect NK-cell responses during primary HIV-1 infection. The phenotypes and functional capacity of NK cells derived from HIV-1-positive and HIV-1-negative individuals were assessed (N = 42 and N = 40, respectively). HIV-1 infection was associated with an increased frequency of KIR2DL1-3(+) NK cells. Further analysis showed that KIR2DL1(+) NK cells were selectively increased in individuals homozygous for HLA-C2, while HLA-C1-homozygous individuals displayed increased proportions of KIR2DL2/3(+) NK cells. KIR2DL1-3(+) NK cells were furthermore more polyfunctional during primary HIV-1 infection in individuals also encoding for their cognate HLA-C group haplotypes, as measured by degranulation and IFN-γ and TNF-α production. These results identify a novel relationship between HLA-C and KIR2DL(+) NK-cell subsets and demonstrate that HLA-C-mediated licensing modulates NK-cell responses to primary HIV-1 infection.

• Authors: Christian Körner, Mitchell E Granoff, Molly A Amero, Michael N Sirignano, Sagar A Vaidya, Stephanie Jost, Todd M Allen, Eric S Rosenberg, Marcus Altfeld
• Journal: European journal of immunology (Eur J Immunol) Vol. 44 Issue 10 Pg. 2938-48 (Oct 2014) ISSN: 1521-4141 [Electronic] Germany
• PMID: 25043727 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• HLA-C Antigens
• KIR2DL1 protein, human
• KIR2DL2 protein, human
• KIR2DL3 protein, human
• Receptors, KIR2DL1
• Receptors, KIR2DL2
• Receptors, KIR2DL3

Topics

• Adult
• Female
• Flow Cytometry
• HIV Infections (genetics, immunology)
• HLA-C Antigens (genetics, immunology)
• Haplotypes
• Humans
• Killer Cells, Natural (immunology)
• Lymphocyte Subsets (immunology)
• Male
• Middle Aged
• Receptors, KIR2DL1 (immunology)
• Receptors, KIR2DL2 (immunology)
• Receptors, KIR2DL3 (immunology)