PMID- 33203899 OWN - NLM STAT- MEDLINE DCOM- 20210114 LR - 20240331 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 10 IP - 1 DP - 2020 Nov 17 TI - Epstein-Barr virus peptides derived from latent cycle proteins alter NKG2A + NK cell effector function. PG - 19973 LID - 10.1038/s41598-020-76344-3 [doi] LID - 19973 AB - 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 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. FAU - Mbiribindi, Berenice AU - Mbiribindi B AD - Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. FAU - Pena, Josselyn K AU - Pena JK AD - Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. FAU - Arvedson, Matthew P AU - Arvedson MP AD - Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. FAU - Moreno Romero, Claudia AU - Moreno Romero C AD - Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. FAU - McCarthy, Sarah R AU - McCarthy SR AD - Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. FAU - Hatton, Olivia L AU - Hatton OL AD - Department of Molecular Biology, Colorado College, Colorado Springs, CO, USA. FAU - Esquivel, Carlos O AU - Esquivel CO AD - Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. FAU - Martinez, Olivia M AU - Martinez OM AD - Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. FAU - Krams, Sheri M AU - Krams SM AD - Division of Abdominal Transplantation, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA. smkrams@stanford.edu. LA - eng GR - U01 AI135950/AI/NIAID NIH HHS/United States GR - T32 AI007290/AI/NIAID NIH HHS/United States GR - U01 AI135947/AI/NIAID NIH HHS/United States GR - S10 RR027431/RR/NCRR NIH HHS/United States GR - U01 AI104342/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20201117 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (KLRC1 protein, human) RN - 0 (Ligands) RN - 0 (NK Cell Lectin-Like Receptor Subfamily C) RN - 0 (Peptides) SB - IM MH - B-Lymphocytes/metabolism MH - Cell Line MH - Herpesvirus 4, Human/*metabolism MH - Histocompatibility Antigens Class I/metabolism MH - Humans MH - Killer Cells, Natural/*metabolism MH - Latent Infection/*metabolism MH - Ligands MH - NK Cell Lectin-Like Receptor Subfamily C/*metabolism MH - Peptides/metabolism PMC - PMC7673117 COIS- The authors declare no competing interests. EDAT- 2020/11/19 06:00 MHDA- 2021/01/15 06:00 PMCR- 2020/11/17 CRDT- 2020/11/18 05:53 PHST- 2020/09/01 00:00 [received] PHST- 2020/10/21 00:00 [accepted] PHST- 2020/11/18 05:53 [entrez] PHST- 2020/11/19 06:00 [pubmed] PHST- 2021/01/15 06:00 [medline] PHST- 2020/11/17 00:00 [pmc-release] AID - 10.1038/s41598-020-76344-3 [pii] AID - 76344 [pii] AID - 10.1038/s41598-020-76344-3 [doi] PST - epublish SO - Sci Rep. 2020 Nov 17;10(1):19973. doi: 10.1038/s41598-020-76344-3.