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Enhanced In Vitro Potency and In Vivo Immunogenicity of a CTL Epitope from Hepatitis C Virus Core Protein following Amino Acid Replacement at Secondary HLA-A2.1 Binding Positions (from Journal of Clinical Investigation 1998, 102 (6), 1239-1248)
Bibliografi
Author:
Sarobe, Pablo
;
Pendleton, C. David
;
Akatsuka, Toshitaka
;
Lau, Daryl
;
Engelhard, Victor H.
;
Feinstone, Stephen M.
;
Berzofsky, Jay A.
Topik:
Cytotoxic T lymphocyte
;
Epitope enhancement
;
Major histocompatibility complex class I affinity
;
Peptide
;
synthetic
;
Vaccine
;
Validation ref - 6
Bahasa:
(EN )
Penerbit:
The American Society for Clinical Investigation, Inc.
Tahun Terbit:
1998
Jenis:
Article - diterbitkan di jurnal ilmiah internasional
Fulltext:
JCI3714.pdf
(290.68KB;
0 download
)
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Abstract
HCV) is often unable to clear the infection, to enhance immunogenicity we studied substituted peptides from an HCV cytotoxic T lymphocyte (CTL) epitope (C7A2) from a conserved region of the HCV core protein (DLMGYIPLV) recognized by CTL lines from HLA-A2.1 HCV-infected patients and HLA-A2.1 transgenic mice. HLA-A2.1 binding, human and murine CTL recognition, and in vivo immunogenicity (using mice transgenic for human HLA-A2 in lieu of immunizing humans) were analyzed to define peptides with enhanced immunogenicity. Peptides substituted at position 1 showed enhanced HLA-A2 binding affinity, but paradoxically poorer immunogenicity. A peptide with Ala substituted at position 8 (8A) showed higher HLA-A2 binding affinity and CTL recognition and was a more potent in vivo immunogen in HLA-A2-transgenic mice, inducing higher CTL responses with higher avidity against native C7A2 than induced by C7A2 itself. These results suggest that peptide 8A is a more potent in vitro antigen and in vivo immunogen than C7A2 and may be useful as a vaccine component. They provide proof of principle that the strategy of epitope enhancement can enhance immunogenicity of a CTL epitope recognized by human CTL.
[validation ref - 6]
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