PMID- 35464415
OWN - NLM
STAT- MEDLINE
DCOM- 20220426
LR  - 20220716
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Screening and Identification of HBV Epitopes Restricted by Multiple Prevalent 
      HLA-A Allotypes.
PG  - 847105
LID - 10.3389/fimmu.2022.847105 [doi]
LID - 847105
AB  - Although host T cell immune responses to hepatitis B virus (HBV) have been 
      demonstrated to have important influences on the outcome of HBV infection, the 
      development of T cell epitope-based vaccine and T cell therapy and the clinical 
      evaluation of specific T cell function are currently hampered markedly by the 
      lack of validated HBV T cell epitopes covering broad patients. This study aimed 
      to screen T cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins 
      and presenting by thirteen prevalent human leukocyte antigen (HLA)-A allotypes 
      which gather a total gene frequency of around 95% in China and Northeast Asia 
      populations. 187 epitopes were in silico predicted. Of which, 62 epitopes were 
      then functionally validated as real-world HBV T cell epitopes by ex vivo IFN-gamma 
      ELISPOT assay and in vitro co-cultures using peripheral blood mononuclear cells 
      (PBMCs) from HBV infected patients. Furthermore, the HLA-A cross-restrictions of 
      each epitope were identified by peptide competitive binding assay using 
      transfected HMy2.CIR cell lines, and by HLA-A/peptide docking as well as 
      molecular dynamic simulation. Finally, a peptide library containing 105 validated 
      epitopes which cross-binding by 13 prevalent HLA-A allotypes were used in ELISPOT 
      assay to enumerate HBV-specific T cells for 116 patients with HBV infection. The 
      spot forming units (SFUs) was significantly correlated with serum HBsAg level as 
      confirmed by multivariate linear regression analysis. This study functionally 
      validated 62 T cell epitopes from HBV main proteins and elucidated their HLA-A 
      restrictions and provided an alternative ELISPOT assay using validated epitope 
      peptides rather than conventional overlapping peptides for the clinical 
      evaluation of HBV-specific T cell responses.
CI  - Copyright (c) 2022 Ding, Zhou, Li, Zhao, Jin, Liu, Wu, Mei, Li, Qiu and Shen.
FAU - Ding, Yan
AU  - Ding Y
AD  - Department of Microbiology and Immunology, Medical School, Southeast University, 
      Nanjing, China.
FAU - Zhou, Zining
AU  - Zhou Z
AD  - Department of Microbiology and Immunology, Medical School, Southeast University, 
      Nanjing, China.
FAU - Li, Xingyu
AU  - Li X
AD  - Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, 
      School of Life Science and Technology, Southeast University, Nanjing, China.
FAU - Zhao, Chen
AU  - Zhao C
AD  - Department of Microbiology and Immunology, Medical School, Southeast University, 
      Nanjing, China.
FAU - Jin, Xiaoxiao
AU  - Jin X
AD  - Department of Microbiology and Immunology, Medical School, Southeast University, 
      Nanjing, China.
FAU - Liu, Xiaotao
AU  - Liu X
AD  - Department of Microbiology and Immunology, Medical School, Southeast University, 
      Nanjing, China.
FAU - Wu, Yandan
AU  - Wu Y
AD  - Department of Microbiology and Immunology, Medical School, Southeast University, 
      Nanjing, China.
FAU - Mei, Xueyin
AU  - Mei X
AD  - Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, 
      School of Life Science and Technology, Southeast University, Nanjing, China.
FAU - Li, Jian
AU  - Li J
AD  - Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, 
      School of Life Science and Technology, Southeast University, Nanjing, China.
FAU - Qiu, Jie
AU  - Qiu J
AD  - Division of Hepatitis, Nanjing Second Hospital, Nanjing Hospital Affiliated to 
      Nanjing University of Chinese Medicine, Nanjing, China.
FAU - Shen, Chuanlai
AU  - Shen C
AD  - Department of Microbiology and Immunology, Medical School, Southeast University, 
      Nanjing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220407
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Hepatitis B Surface Antigens)
RN  - 0 (Peptides)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Epitopes, T-Lymphocyte
MH  - HLA-A Antigens
MH  - *Hepatitis B
MH  - Hepatitis B Surface Antigens
MH  - *Hepatitis B virus
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Leukocytes, Mononuclear
MH  - Peptides
PMC - PMC9021956
OTO - NOTNLM
OT  - ELISPOT
OT  - HLA-A
OT  - T cell epitope
OT  - antigen-specific T cell detection
OT  - bioinformatics analysis
OT  - hepatitis B virus
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/26 06:00
MHDA- 2022/04/27 06:00
PMCR- 2022/01/01
CRDT- 2022/04/25 05:33
PHST- 2022/01/01 00:00 [received]
PHST- 2022/03/15 00:00 [accepted]
PHST- 2022/04/25 05:33 [entrez]
PHST- 2022/04/26 06:00 [pubmed]
PHST- 2022/04/27 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.847105 [doi]
PST - epublish
SO  - Front Immunol. 2022 Apr 7;13:847105. doi: 10.3389/fimmu.2022.847105. eCollection 
      2022.