PMID- 27551282
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160823
LR  - 20181113
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 7
DP  - 2016
TI  - Structure and Function of HLA-A*02-Restricted Hantaan Virus Cytotoxic T-Cell 
      Epitope That Mediates Effective Protective Responses in HLA-A2.1/K(b) Transgenic 
      Mice.
PG  - 298
LID - 10.3389/fimmu.2016.00298 [doi]
LID - 298
AB  - Hantavirus infections cause severe emerging diseases in humans and are associated 
      with high mortality rates; therefore, they have become a global public health 
      concern. Our previous study showed that the CD8(+) T-cell epitope aa129-aa137 
      (FVVPILLKA, FA9) of the Hantaan virus (HTNV) nucleoprotein (NP), restricted by 
      human leukocyte antigen (HLA)-A*02, induced specific CD8(+) T-cell responses that 
      controlled HTNV infection in humans. However, the in vivo immunogenicity of 
      peptide FA9 and the effect of FA9-specific CD8(+) T-cell immunity remain unclear. 
      Here, based on a detailed structural analysis of the peptide FA9/HLA-A*0201 
      complex and functional investigations using HLA-A2.1/K(b) transgenic (Tg) mice, 
      we found that the overall structure of the peptide FA9/HLA-A*0201 complex 
      displayed a typical MHC class I fold with Val2 and Ala9 as primary anchor 
      residues and Val3 and Leu7 as secondary anchor residues that allow peptide FA9 to 
      bind tightly with an HLA-A*0201 molecule. Residues in the middle portion of 
      peptide FA9 extruding out of the binding groove may be the sites that allow for 
      recognition by T-cell receptors. Immunization with peptide FA9 in HLA-A2.1/K(b) 
      Tg mice induced FA9-specific cytotoxic T-cell responses characterized by the 
      induction of high expression levels of interferon-gamma, tumor necrosis factor-alpha, 
      granzyme B, and CD107a. In an HTNV challenge trial, significant reductions in the 
      levels of both the antigens and the HTNV RNA loads were observed in the liver, 
      spleen, and kidneys of Tg mice pre-vaccinated with peptide FA9. Thus, our 
      findings highlight the ability of HTNV epitope-specific CD8(+) T-cell immunity to 
      control HTNV and support the possibility that the HTNV-NP FA9 peptide, naturally 
      processed in vivo in an HLA-A*02-restriction manner, may be a good candidate for 
      the development HTNV peptide vaccines.
FAU - Ma, Ying
AU  - Ma Y
AD  - Department of Immunology, The Fourth Military Medical University , Xi'an , China.
FAU - Cheng, Linfeng
AU  - Cheng L
AD  - Department of Microbiology, The Fourth Military Medical University , Xi'an , 
      China.
FAU - Yuan, Bin
AU  - Yuan B
AD  - Institute of Orthopaedics of Xijing Hospital, The Fourth Military Medical 
      University , Xi'an , China.
FAU - Zhang, Yusi
AU  - Zhang Y
AD  - Department of Immunology, The Fourth Military Medical University , Xi'an , China.
FAU - Zhang, Chunmei
AU  - Zhang C
AD  - Department of Immunology, The Fourth Military Medical University , Xi'an , China.
FAU - Zhang, Yun
AU  - Zhang Y
AD  - Department of Immunology, The Fourth Military Medical University , Xi'an , China.
FAU - Tang, Kang
AU  - Tang K
AD  - Department of Immunology, The Fourth Military Medical University , Xi'an , China.
FAU - Zhuang, Ran
AU  - Zhuang R
AD  - Department of Immunology, The Fourth Military Medical University , Xi'an , China.
FAU - Chen, Lihua
AU  - Chen L
AD  - Department of Immunology, The Fourth Military Medical University , Xi'an , China.
FAU - Yang, Kun
AU  - Yang K
AD  - Department of Immunology, The Fourth Military Medical University , Xi'an , China.
FAU - Zhang, Fanglin
AU  - Zhang F
AD  - Department of Microbiology, The Fourth Military Medical University , Xi'an , 
      China.
FAU - Jin, Boquan
AU  - Jin B
AD  - Department of Immunology, The Fourth Military Medical University , Xi'an , China.
LA  - eng
PT  - Journal Article
DEP - 20160808
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC4976285
OTO - NOTNLM
OT  - CD8+ T-cell response
OT  - HLA-A*02
OT  - HLA-A2.1/Kb transgenic mice
OT  - Hantaan virus
OT  - crystal structure
OT  - cytotoxic T-cell epitope
EDAT- 2016/08/24 06:00
MHDA- 2016/08/24 06:01
PMCR- 2016/01/01
CRDT- 2016/08/24 06:00
PHST- 2016/06/27 00:00 [received]
PHST- 2016/07/22 00:00 [accepted]
PHST- 2016/08/24 06:00 [entrez]
PHST- 2016/08/24 06:00 [pubmed]
PHST- 2016/08/24 06:01 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2016.00298 [doi]
PST - epublish
SO  - Front Immunol. 2016 Aug 8;7:298. doi: 10.3389/fimmu.2016.00298. eCollection 2016.