Article ; Online: HLA-C-restricted viral epitopes are associated with an escape mechanism from KIR2DL2
2019 Volume 40, Page(s) 605–613
Abstract: Background: Lassa virus (LASV) is the etiologic agent of an acute hemorrhagic fever endemic in West Africa. Natural killer (NK) cells control viral infections in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and ... ...
| Abstract | Background: Lassa virus (LASV) is the etiologic agent of an acute hemorrhagic fever endemic in West Africa. Natural killer (NK) cells control viral infections in part through the interaction between killer cell immunoglobulin-like receptors (KIRs) and their ligands. LASV infection is associated with defective immune responses, including inhibition of NK cell activity in the presence of MHC-class 1 Methods: We compared individual KIR and HLA-class 1 genotypes of 68 healthy volunteers to 51 patients infected with LASV in Sierra Leone, including 37 survivors and 14 fatalities. Next, potential HLA-C1, HLA-C2, and HLA-Bw4 binding epitopes were in silico screened among LASV nucleoprotein (NP) and envelope glycoprotein (GP). Selected 10-mer peptides were then tested in peptide-HLA stabilization, KIR binding and polyfunction assays. Findings: LASV-infected patients were similar to healthy controls, except for the inhibitory KIR2DL2 gene. We found a specific increase in the HLA-C1:KIR2DL2 interaction in fatalities (10/11) as compared to survivors (12/19) and controls (19/29). We also identified that strong of NP and GP viral epitopes was only observed with HLA-C molecules, and associated with strong inhibition of degranulation in the presence of KIR2DL Interpretation: Our finding suggests that presentation of specific LASV epitopes by HLA-C alleles to the inhibitory KIR2DL2 receptor on NK cells could potentially prevent the killing of infected cells and provides insights into the mechanisms by which LASV can escape NK-cell-mediated immune pressure. |
|---|---|
| MeSH term(s) | Antigens, Viral/immunology ; Cell Line ; Cytotoxicity, Immunologic ; Epitope Mapping/methods ; Epitopes/immunology ; Genotype ; HLA-C Antigens/genetics ; HLA-C Antigens/immunology ; Humans ; Immune Tolerance ; Immunomodulation ; Immunophenotyping ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Lassa Fever/genetics ; Lassa Fever/immunology ; Lassa Fever/metabolism ; Lassa Fever/virology ; Lassa virus/immunology ; Protein Binding ; Receptors, KIR2DL2/genetics ; Receptors, KIR2DL2/metabolism |
| Chemical Substances | Antigens, Viral ; Epitopes ; HLA-C Antigens ; KIR2DL2 protein, human ; Receptors, KIR2DL2 |
| Language | English |
| Publishing date | 2019-01-30 |
| Publishing country | Netherlands |
| Document type | Journal Article |
| ZDB-ID | 2851331-9 |
| ISSN | 2352-3964 |
| ISSN (online) | 2352-3964 |
| DOI | 10.1016/j.ebiom.2019.01.048 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Zs.A 7090: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.