Epstein-Barr Virus Peptides Derived from Latent Cycle Proteins Prevent the Inhibition of NKG2A Expressing NK Cells
45 Pages Posted: 20 Apr 2020 Sneak Peek Status: Under ReviewMore...
Natural killer (NK) cells control viral infection through the interaction between inhibitory receptors and human leukocyte antigen (HLA) ligands and bound peptide. NK cells expressing the inhibitory receptor NKG2A/CD94 recognize and respond to autologous B cells latently infected with Epstein–Barr virus (EBV). The mechanism is not yet understood, thus we investigated peptides derived from the seven latent proteins of EBV in the interaction of NKG2A and its ligand HLA-E. Functional analysis demonstrated that EBV peptides can bind to HLA-E and block inhibition of NK cell effector function. Moreover, analysis of DNA from 79 subjects showed sequence variations in the latent protein, LMP1, which alters NK responses to EBV. We provide evidence that peptides derived from EBV latent cycle proteins can impair the recognition of NKG2A despite being presented by HLA-E, resulting in NK cell activation. Thus, blocking of the NKG2A-HLA-E axis with viral peptides may have therapeutic potential.
Keywords: NK cells, EBV, peptide presentation, HLA-E, NKG2A
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