T-helper epitopes identified within the E6 transforming protein of cervical cancer-associated human papillomavirus type 16

Viral Immunol. 1999;12(4):297-312. doi: 10.1089/vim.1999.12.297.


The E6 oncoprotein of human papillomavirus type 16 (HPV16 E6) produced by tumor cells of HPV16-associated cervical carcinoma is poorly immunogenic in patients, but nonetheless is a tumor-specific antigen to which therapeutic vaccine strategies may be directed. To investigate the subunit immunogenicity of E6 protein at the T-helper cell level, we immunized mice with overlapping peptides spanning the entire 158 amino acid sequence. Two peptides recalled a proliferative response in lymph node cells (LNC) from C57BL/6 (H-2b)-immunized mice. One of these peptides also recalled proliferative responses in the context of 5/5 other major histocompatibility complex (MHC) class II haplotypes, indicating a "promiscuous" T-epitope. Minimal consensus motif analysis identified the epitopes as 60VYRDGNPYA68 and 98GYNKPLCDLL107. LNC from mice immunized with T-epitope proliferated in response to challenge with whole E6 protein. Immunization with E6 T-epitopes linked to B-epitopes of HPV16 E7 protein elicited specific antibody indicating that T-cells recognizing the T-epitopes provided cognate "help" for B-cells. LNC from mice co-immunized with E6 T-epitope and the major T-helper epitope of HPV16 E7 (48DRAHYNI54) proliferated comparably when challenged with the peptides individually indicating co-dominance of the two T-epitopes. The findings have implications for incorporation of E6 into a therapeutic vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • B-Lymphocytes / immunology
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immunization
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / chemistry
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / immunology*
  • Papillomaviridae / immunology*
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections / immunology
  • Papillomavirus Infections / virology
  • Peptides / chemical synthesis
  • Peptides / immunology
  • Repressor Proteins*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Tumor Virus Infections / immunology
  • Tumor Virus Infections / virology
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / virology*
  • Viral Vaccines / immunology


  • E6 protein, Human papillomavirus type 16
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Peptides
  • Repressor Proteins
  • Viral Vaccines
  • oncogene protein E7, Human papillomavirus type 16