Cytotoxic T-lymphocyte responses to human papillomavirus type 16 E5 and E7 proteins and HLA-A*0201-restricted T-cell peptides in cervical cancer patients

Dai Wei Liu, Yuh Cheng Yang, Ho Fan Lin, Mei Fang Lin, Ya Wen Cheng, Chen Ng Chu, Yeou Ping Tsao, Show Li Chen

Research output: Contribution to journalArticle

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Abstract

Previously, we found that human papillomavirus type 16 (HPV-16) E5 protein is a tamor rejection antigen and can induce cytotoxic T-lymphocyte (CTL) activity. Therefore, in this study, human leukocyte antigen A*0201 (HLA-A*0201)-restricted human CTL epitopes of HPV-16 E5 protein were identified using a bioinformatics approach, and the abilities of these predicted peptides to induce an immune response in HLA-A*0201 transgenic mice were confirmed by assaying E5-specific CTLs and in vitro-generated CTLs from normal peripheral blood T lymphocytes of HLA-A2-positive human donors. Second, the CTL responses to HLA-A*0201 CTL epitopes (E5 63-71 and E7 11-20) were examined in HPV-16-infected patients with HLA-A2. Third, the effect of HLA-A-type alleles on CTL activities in response to the entire E5 and E7 proteins was examined in cervical cancer patients. E5 and E7 peptides (but not the whole proteins) stimulated E5- and E7-specific CTL recall responses in HPV-16- and HLA-A2-positive cervical cancer patients, and HPV-16 E5 and E7 proteins stimulated naïve T cells in HPV-16-megative cervical cancer patients with HLA-A11 and -A24 haplotypes. In summary, this is the first demonstration that E5 63-71 is an HLA-A*0201-restricted T-cell epitope of HPV-16 E5.

Original languageEnglish
Pages (from-to)2869-2879
Number of pages11
JournalJournal of Virology
Volume81
Issue number6
DOIs
Publication statusPublished - Mar 2007
Externally publishedYes

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Papillomavirus E7 Proteins
cytotoxic T-lymphocytes
uterine cervical neoplasms
Papillomaviridae
Cytotoxic T-Lymphocytes
HLA Antigens
Uterine Cervical Neoplasms
Human papillomavirus 16
T-lymphocytes
peptides
T-Lymphocytes
HLA-A2 Antigen
Peptides
T-Lymphocyte Epitopes
proteins
epitopes
HLA-A11 Antigen
HLA-A24 Antigen
HLA-A Antigens
Computational Biology

ASJC Scopus subject areas

  • Immunology

Cite this

Cytotoxic T-lymphocyte responses to human papillomavirus type 16 E5 and E7 proteins and HLA-A*0201-restricted T-cell peptides in cervical cancer patients. / Liu, Dai Wei; Yang, Yuh Cheng; Lin, Ho Fan; Lin, Mei Fang; Cheng, Ya Wen; Chu, Chen Ng; Tsao, Yeou Ping; Chen, Show Li.

In: Journal of Virology, Vol. 81, No. 6, 03.2007, p. 2869-2879.

Research output: Contribution to journalArticle

Liu, Dai Wei ; Yang, Yuh Cheng ; Lin, Ho Fan ; Lin, Mei Fang ; Cheng, Ya Wen ; Chu, Chen Ng ; Tsao, Yeou Ping ; Chen, Show Li. / Cytotoxic T-lymphocyte responses to human papillomavirus type 16 E5 and E7 proteins and HLA-A*0201-restricted T-cell peptides in cervical cancer patients. In: Journal of Virology. 2007 ; Vol. 81, No. 6. pp. 2869-2879.
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abstract = "Previously, we found that human papillomavirus type 16 (HPV-16) E5 protein is a tamor rejection antigen and can induce cytotoxic T-lymphocyte (CTL) activity. Therefore, in this study, human leukocyte antigen A*0201 (HLA-A*0201)-restricted human CTL epitopes of HPV-16 E5 protein were identified using a bioinformatics approach, and the abilities of these predicted peptides to induce an immune response in HLA-A*0201 transgenic mice were confirmed by assaying E5-specific CTLs and in vitro-generated CTLs from normal peripheral blood T lymphocytes of HLA-A2-positive human donors. Second, the CTL responses to HLA-A*0201 CTL epitopes (E5 63-71 and E7 11-20) were examined in HPV-16-infected patients with HLA-A2. Third, the effect of HLA-A-type alleles on CTL activities in response to the entire E5 and E7 proteins was examined in cervical cancer patients. E5 and E7 peptides (but not the whole proteins) stimulated E5- and E7-specific CTL recall responses in HPV-16- and HLA-A2-positive cervical cancer patients, and HPV-16 E5 and E7 proteins stimulated na{\"i}ve T cells in HPV-16-megative cervical cancer patients with HLA-A11 and -A24 haplotypes. In summary, this is the first demonstration that E5 63-71 is an HLA-A*0201-restricted T-cell epitope of HPV-16 E5.",
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