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Citations to this article

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.
P Sarobe, … , S M Feinstone, J A Berzofsky
P Sarobe, … , S M Feinstone, J A Berzofsky
Published September 15, 1998
Citation Information: J Clin Invest. 1998;102(6):1239-1248. https://doi.org/10.1172/JCI3714.
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Research Article Article has an altmetric score of 9

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.

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Abstract

Since the natural immune response to hepatitis C virus (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.

Authors

P Sarobe, C D Pendleton, T Akatsuka, D Lau, V H Engelhard, S M Feinstone, J A Berzofsky

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Total citations by year

Year: 2022 2018 2017 2016 2013 2012 2011 2010 2009 2008 2007 2006 2005 2004 2003 2002 2001 2000 1999 Total
Citations: 4 1 1 2 2 1 2 2 3 3 2 5 4 7 9 6 10 6 5 75
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Citations to this article in year 2004 (7)

Title and authors Publication Year
Progress on new vaccine strategies against chronic viral infections
JA Berzofsky, JD Ahlers, J Janik, J Morris, SK Oh, M Terabe, IM Belyakov
Journal of Clinical Investigation 2004
Protection against Lethal Vaccinia Virus Challenge in HLA-A2 Transgenic Mice by Immunization with a Single CD8 + T-Cell Peptide Epitope of Vaccinia and Variola Viruses
JT Snyder, IM Belyakov, A Dzutsev, F Lemonnier, JA Berzofsky
Journal of virology 2004
Identification of an HLA-A*0201 cytotoxic T lymphocyte epitope specific to the endothelial antigen Tie-2
JM Ramage, R Metheringham, A Conn, I Spendlove, RS Moss, DT Patton, JC Murray, RC Rees, LG Durrant
International Journal of Cancer 2004
Modification of the Inhibitory Amino Acid for Epitope Peptide Binding onto Major Histocompatibility Complex Class II Molecules Enhances Immunogenicity of the Antigen
SH Chang, J Kim, KY Lee, HJ Kim, YJ Chung, CU Park, BS Kim, YS Jang
Scandinavian Journal of Immunology 2004
Cellular Immune Responses in Seronegative Sexual Contacts of Acute Hepatitis C Patients
SM Kamal, A Amin, M Madwar, CS Graham, Q He, AA Tawil, J Rasenack, T Nakano, B Robertson, A Ismail, MJ Koziel
Journal of virology 2004
The HIV-1 HLA-A2-SLYNTVATL Is a Help-Independent CTL Epitope
J Kan-Mitchell, B Bisikirska, F Wong-Staal, KL Schaubert, M Bajcz, M Bereta
Journal of immunology (Baltimore, Md. : 1950) 2004
Human CTLs to Wild-Type and Enhanced Epitopes of a Novel Prostate and Breast Tumor-Associated Protein, TARP, Lyse Human Breast Cancer Cells
SK Oh, M Terabe, CD Pendleton, A Bhattacharyya, TK Bera, M Epel, Y Reiter, J Phillips, WM Linehan, C Kasten-Sportes, I Pastan, JA Berzofsky
Cancer research 2004

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