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  • Title: A single amino acid substitution improves the in vivo immunogenicity of the HPV16 oncoprotein E7(11-20) cytotoxic T lymphocyte epitope.
    Author: Schreurs MW, Kueter EW, Scholten KB, Lemonnier FA, Meijer CJ, Hooijberg E.
    Journal: Vaccine; 2005 Jul 01; 23(31):4005-10. PubMed ID: 15963358.
    Abstract:
    One of the few and most extensively studied human papilloma virus (HPV) type 16 oncoprotein E7-derived cytotoxic T lymphocyte (CTL) epitopes is YMLDLQPETT, presented to CTL by HLA-A2.1. We previously identified an altered peptide ligand (APL) of this epitope with increased binding affinity for HLA-A2.1, YMLDLQPETV. Herein, the in vivo immunogenicity of this APL was investigated in HLA-A2.1 transgenic HHD mice. Both in vitro and direct ex vivo analysis, performed using newly generated HHD tetramers, showed a significant increase in the number of specific CD8+ T cells upon vaccination with the APL as compared to its unmodified counterpart. Improved immunogenicity of the APL was also observed in functional analyses, including antigen-specific lytic activity and cytokine production of primed CD8+ T cells. Consequently, the YMLDLQPETV peptide may prove useful when included in vaccination strategies against HPV16-induced cervical carcinoma.
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