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Vaccine. 2005 Jul 1;23(31):4005-10. Epub 2005 Apr 11.

A single amino acid substitution improves the in vivo immunogenicity of the HPV16 oncoprotein E7(11-20) cytotoxic T lymphocyte epitope.

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Department of Pathology, VU University Medical Center, de Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.


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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