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Journal of Virology, March 2007, p. 2869-2879, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.02256-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Dai-Wei Liu,2,3,{dagger} Yuh-Cheng Yang,7,8,9,{dagger} Ho-Fan Lin,4,{dagger} Mei-Fang Lin,4 Ya-Wen Cheng,5 Chen-Chung Chu,7 Yeou-Ping Tsao,6,7 and Show-Li Chen1,4*

Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan,1 Department of Radiation Oncology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan,2 Department of Radiology, Tzu Chi University, Hualien, Taiwan,3 Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan,4 Department of Medicine, Chung Shan Medical University, Taichung, Taiwan,5 Department of Ophthalmology,6 Department of Medical Research, Mackay Memorial Hospital,7 Mackay Medicine, Nursing, and Management College,8 Taipei Medical University, Taipei, Taiwan9

Received 14 October 2006/ Accepted 13 December 2006

Previously, we found that human papillomavirus type 16 (HPV-16) E5 protein is a tumor 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-negative 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.

* Corresponding author. Mailing address: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, 7F, No. 1, Sec. 1, Jen-Ai Rd., Taipei, Taiwan. Phone: 886-2-23123456, ext. 8289. Fax: 886-2-2391-5293. E-mail: showlic{at}ha.mc.ntu.edu.tw.

{triangledown} Published ahead of print on 3 January 2007.

{dagger} D.-W.L., Y.-C.Y., and H.-F.L. contributed equally to this work.

Journal of Virology, March 2007, p. 2869-2879, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.02256-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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