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.
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.
Liu
Dai-Wei
DW
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, 7F, No. 1 Sec. 1 Jen-Ai Rd., Taipei, Taiwan.
Yang
Yuh-Cheng
YC
Lin
Ho-Fan
HF
Lin
Mei-Fang
MF
Cheng
Ya-Wen
YW
Chu
Chen-Chung
CC
Tsao
Yeou-Ping
YP
Chen
Show-Li
SL
D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D000483:Alleles; D000818:Animals; D002277:Carcinoma / Q000473:pathology; D000939:Epitopes; D005260:Female; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology*
D000939:Epitopes; D015234:HLA-A Antigens; D009856:Oncogene Proteins, Viral; D007371:Interferon-gamma