A PUBLIC T-HELPER EPITOPE OF THE E7 TRANSFORMING PROTEIN OF HUMAN PAPILLOMAVIRUS-16 PROVIDES COGNATE HELP FOR SEVERAL E7 B-CELL EPITOPES FROM CERVICAL CANCER-ASSOCIATED HUMAN PAPILLOMAVIRUS GENOTYPES

被引:172
作者
TINDLE, RW [1 ]
FERNANDO, GJP [1 ]
STERLING, JC [1 ]
FRAZER, IH [1 ]
机构
[1] UNIV CAMBRIDGE, DEPT VIROL, CAMBRIDGE CB2 1QP, ENGLAND
关键词
ANTIBODY; T-CELL-B-CELL COOPERATION; SUBUNIT VACCINE; SYNTHETIC PEPTIDES;
D O I
10.1073/pnas.88.13.5887
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have identified a major T-cell epitope, amino acids 48-54 (DRAHYNI, in one-letter code) in the E7 open reading frame protein of human papillomavirus (HPV) type 16. Lymph node cells from mice immunized with synthetic peptides containing DRAHYNI proliferated and produced interleukin when challenged in vitro with peptide or whole HPV-16 E7 fusion protein. The T epitope was recognized in association with all five major histocompatibility complex class II I-A and I-E alleles tested. Synthetic peptides consisting of DRAHYNI linked to major B-cell epitopes on the E7 molecule formed immunogens capable of eliciting strong antibody responses to HPV-16 E7. The T epitope could provide help for the production of antibody to several B epitopes simultaneously, including a B epitope of HPV-18 E7 protein. Mice immunized with a peptide containing DRAHYNI and B epitope and, at a later date, infected with recombinant vaccinia E7 virus, displayed secondary antibody responses to E7. Because E7 has a role in cell transformation and is the most abundant viral protein in HPV-associated neoplastic cervical epithelial cells, the data have implications for vaccine strategies.
引用
收藏
页码:5887 / 5891
页数:5
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