About: 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

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About: 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 Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	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
Creator	Ma, Ying Cheng, Linfeng Jin, Boquan Tang, Kang Zhang, Chunmei Zhang, Fanglin Zhang, Yun Zhang, Yusi Zhuang, Ran Yang, Kun Chen, Lihua Cn, Boquan, Jin Morrot, Alexandre
Source	Medline; PMC
abstract	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)-A02, 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-A0201 complex and functional investigations using HLA-A2.1/K(b) transgenic (Tg) mice, we found that the overall structure of the peptide FA9/HLA-A0201 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-A0201 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-γ, tumor necrosis factor-α, 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.
has issue date	2016-08-08(xsd:dateTime)
bibo:doi	10.3389/fimmu.2016.00298
bibo:pmid	27551282
has license	cc-by
sha1sum (hex)	729e5d420ec1a80d31928dc8bb261610a93aa890
schema:url	https://doi.org/10.3389/fimmu.2016.00298
resource representing a document's title	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
has PubMed Central identifier	PMC4976285
has PubMed identifier	27551282
schema:publication	Front Immunol
resource representing a document's body	covid:729e5d420ec1a80d31928dc8bb261610a93aa890#body_text
is schema:about of	named entity 'HLA-A2' named entity 'induction' named entity 'kidneys' named entity 'immunogenicity' named entity 'transgenic' named entity 'anchor' named entity 'T-cell receptors' named entity 'Our' named entity 'Transgenic' named entity 'STRUCTURE' covid:arg/729e5d420ec1a80d31928dc8bb261610a93aa890 named entity 'MIDDLE' named entity 'HANTAVIRUS INFECTIONS' named entity 'FOLD' named entity 'TUMOR NECROSIS FACTOR' named entity 'REDUCTIONS' named entity 'LEU7' named entity 'LEVELS' named entity 'CYTOTOXIC T-CELL' named entity 'PORTION' named entity 'INDUCED' named entity 'KIDNEYS' named entity 'DETAILED' named entity 'STUDY' named entity 'RNA' named entity 'HAVE' named entity 'LIVER' named entity 'GRANZYME B' named entity 'MAY BE' named entity 'MOLECULE' named entity 'RESPONSES' named entity 'PREVIOUS' named entity 'RECOGNITION' named entity 'INVESTIGATIONS' named entity 'FINDINGS' named entity 'GROOVE' named entity 'BIND' named entity 'CAUSE' named entity 'SIGNIFICANT' named entity 'OVERALL' named entity 'HIGH' named entity 'EFFECT' named entity 'EPITOPE' named entity 'ABILITY' named entity 'ALA9' named entity 'MORTALITY RATES' named entity 'HERE' named entity 'RESTRICTION' named entity 'CONTROLLED' named entity 'NUCLEOPROTEIN' named entity 'HLA-A2' named entity 'DISEASES' named entity 'SPLEEN' named entity 'UNCLEAR' named entity 'VACCINATED' named entity 'OBSERVED' named entity 'VAL3' named entity 'DISPLAYED' named entity 'IMMUNIZATION' named entity 'MHC CLASS I' named entity 'TYPICAL' named entity 'HANTAAN VIRUS' named entity 'BASED' named entity 'CD107A' named entity 'CD8' named entity 'PRE' named entity 'CANDIDATE' named entity 'USING'

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