A conserved HIV-1-derived peptide presented by HLA-E renders infected T-cells highly susceptible to attack by NKG2A/CD94-bearing natural killer cells
- Author(s)
- Davis, ZB; Cogswell, A; Scott, H; Mertsching, A; Boucau, J; Wambua, D; Le Gall, S; Planelles, V; Campbell, KS; Barker, E;
- Details
- Publication Year 2016-02,Volume 12,Issue #2,Page e1005421
- Journal Title
- PLoS Pathog
- Publication Type
- Journal Article
- Abstract
- Major histocompatibility class I (MHC-I)-specific inhibitory receptors on natural killer (NK) cells (iNKRs) tolerize mature NK cell responses toward normal cells. NK cells generate cytolytic responses to virus-infected or malignant target cells with altered or decreased MHC-I surface expression due to the loss of tolerizing ligands. The NKG2A/CD94 iNKR suppresses NK cell responses through recognition of the non-classical MHC-I, HLA-E. We used HIV-infected primary T-cells as targets in an in vitro cytolytic assay with autologous NK cells from healthy donors. In these experiments, primary NKG2A/CD94(+) NK cells surprisingly generated the most efficient responses toward HIV-infected T-cells, despite high HLA-E expression on the infected targets. Since certain MHC-I-presented peptides can alter recognition by iNKRs, we hypothesized that HIV-1-derived peptides presented by HLA-E on infected cells may block engagement with NKG2A/CD94, thereby engendering susceptibility to NKG2A/CD94(+) NK cells. We demonstrate that HLA-E is capable of presenting a highly conserved peptide from HIV-1 capsid (AISPRTLNA) that is not recognized by NKG2A/CD94. We further confirmed that HLA-C expressed on HIV-infected cells restricts attack by KIR2DL(+) CD56(dim) NK cells, in contrast to the efficient responses by CD56(bright) NK cells, which express predominantly NKG2A/CD94 and lack KIR2DLs. These findings are important since the use of NK cells was recently proposed to treat latently HIV-1-infected patients in combination with latency reversing agents. Our results provide a mechanistic basis to guide these future clinical studies, suggesting that ex vivo-expanded NKG2A/CD94(+) KIR2DL(-) NK cells may be uniquely beneficial.
- Publisher
- PLOS
- Research Division(s)
- Cell Signalling And Cell Death
- PubMed ID
- 26828202
- Publisher's Version
- https://doi.org/10.1371/journal.ppat.1005421
- Open Access at Publisher's Site
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Creation Date: 2016-08-09 12:01:49
Last Modified: 2016-08-10 10:14:10