PMID- 33658348
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230228
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 95
IP  - 10
DP  - 2021 Apr 26
TI  - T cell epitope screening of Epstein-Barr virus fusion protein gB.
LID - JVI.00081-21 [pii]
LID - 10.1128/JVI.00081-21 [doi]
LID - e00081-21
AB  - Glycoprotein B (gB) is an essential fusion protein for the Epstein-Barr virus 
      (EBV) infection of both B cells and epithelial cells and is thus a promising 
      target antigen for a prophylactic vaccine to prevent or reduce EBV-associated 
      disease. T cell responses play key roles in the control of persistent EBV 
      infection and in the efficacy of a vaccine. However, to date, T cell responses to 
      gB have been characterized for only a limited number of human leukocyte antigen 
      (HLA) alleles. Here, we screened gB T cell epitopes in 23 healthy EBV carriers 
      and ten patients with nasopharyngeal cancer (NPC) using a peptide library 
      spanning the entire gB sequence. We identified twelve novel epitopes in the 
      context of seven new HLA restrictions that are common in Asian populations. Two 
      epitopes, gB(214-223) and gB(840-849), restricted by HLA-B*58:01 and B*38:02, 
      respectively, elicited specific CD8(+) T cell responses to inhibit EBV-driven B 
      cell transformation. Interestingly, gB-specific CD8(+) T cells were more frequent 
      in healthy viral carriers with EBV reactivation than in those without EBV 
      reactivation, indicating that EBV reactivation in vivo stimulates both humoral 
      (VCA-gp125-IgA) and cellular responses to gB. We further found that most gB 
      epitopes are conserved among different EBV strains. Our study broadens the 
      diversity and HLA restrictions of gB epitopes and suggests that gB is a common 
      target of T cell responses in healthy viral carriers with EBV reactivation. In 
      particular, the precisely mapped and conserved gB epitopes provide valuable 
      information for prophylactic vaccine development.ImportanceT cells are crucial 
      for the control of persistent EBV infection and the development of EBV-associated 
      diseases. The EBV gB protein is essential for virus entry into B cells and 
      epithelial cells and is thus a target antigen for vaccine development. 
      Understanding T cell responses to gB is important for subunit vaccine design. 
      Herein, we comprehensively characterized T cell responses to full-length gB. Our 
      results expand the available gB epitopes and HLA restrictions, particularly those 
      common in Asian populations. Furthermore, we showed that gB-specific CD8(+) T 
      cells inhibit B cell transformation ex vivo and that gB-specific CD8(+) T cell 
      responses in vivo may be associated with intermittent EBV reactivation in 
      asymptomatic viral carriers. These gB epitopes are highly conserved among 
      geographically separated EBV strains. Precisely mapped and conserved T cell 
      epitopes may contribute to immune monitoring and to the development of a gB 
      subunit vaccine.
CI  - Copyright (c) 2021 American Society for Microbiology.
FAU - Chen, Haiwen
AU  - Chen H
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China.
FAU - Zhang, Xiao
AU  - Zhang X
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China.
FAU - Zhang, Shanshan
AU  - Zhang S
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China.
FAU - Duan, Xiaobing
AU  - Duan X
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China.
FAU - Xiang, Tong
AU  - Xiang T
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China.
FAU - Zhou, Xiang
AU  - Zhou X
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China.
FAU - Zhang, Wanlin
AU  - Zhang W
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China.
FAU - Zhang, Xinyu
AU  - Zhang X
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China.
FAU - Feng, Qisheng
AU  - Feng Q
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China.
FAU - Kang, Yinfeng
AU  - Kang Y
AD  - Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 
      Guangzhou, P. R. China.
FAU - Li, Jiangping
AU  - Li J
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China.
FAU - Deng, Lan
AU  - Deng L
AD  - Department of Hematology, Zhujiang Hospital, Southern Medical University, 
      Guangzhou, P. R. China.
FAU - Wang, Liang
AU  - Wang L
AD  - Department of Hematology, Beijing Tongren Hospital, Capital Medical University, 
      Beijing, P. R. China.
FAU - Lv, Xing
AU  - Lv X
AD  - Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 
      Guangzhou, P. R. China.
FAU - Zeng, Musheng
AU  - Zeng M
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China.
FAU - Zeng, Yi-Xin
AU  - Zeng YX
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China zengyx@sysucc.org.cn xumiao@sysucc.org.cn.
FAU - Xu, Miao
AU  - Xu M
AD  - State Key Laboratory of Oncology in South China, Collaborative Innovation Center 
      for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma 
      Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. 
      China zengyx@sysucc.org.cn xumiao@sysucc.org.cn.
LA  - eng
PT  - Journal Article
DEP - 20210303
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
SB  - IM
PMC - PMC8139657
EDAT- 2021/03/05 06:00
MHDA- 2021/03/05 06:01
PMCR- 2021/10/26
CRDT- 2021/03/04 05:45
PHST- 2021/03/04 05:45 [entrez]
PHST- 2021/03/05 06:00 [pubmed]
PHST- 2021/03/05 06:01 [medline]
PHST- 2021/10/26 00:00 [pmc-release]
AID - JVI.00081-21 [pii]
AID - 00081-21 [pii]
AID - 10.1128/JVI.00081-21 [doi]
PST - ppublish
SO  - J Virol. 2021 Apr 26;95(10):e00081-21. doi: 10.1128/JVI.00081-21. Epub 2021 Mar 
      3.