title: Evaluation of immunological cross-reactivity between clade A9 high-risk human papillomavirus types on the basis of E6-Specific CD4+ memory T cell responses.
abstract: CD4(+) T cell responses against the E6 oncoprotein of human papillomavirus (HPV) type 16 and 5 closely related members of clade A9 (HPV31, 33, 35, 52, and 58) were charted in peripheral blood mononuclear cell cultures from healthy subjects and patients who underwent HPV16 E6/E7-specific vaccination. Initial analyses with overlapping peptide arrays showed that approximately one-half of the responding subjects displayed reactivity against corresponding E6 peptides from >or=2 HPV types. This suggested immunological cross-reactivity and complicated retrospective evaluation of the infection history of the healthy subjects. Importantly, further dissection of the response by means of enriched and clonal T cell cultures (with protein antigen instead of peptides) revealed that CD4(+) T cells that are capable of efficiently reacting against E6 antigen from multiple HPV types are rare and only occur when epitope sequences are highly conserved. Our data indicate that natural and vaccine-induced HPV16 E6-specific CD4(+) T cell responses are unlikely to mediate efficient cross-protection against other clade A9 members.
authors.affiliation: Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Muriel
authors.initials: M
authors.lastname: van den Hende
authors.forename: Anke
authors.initials: A
authors.lastname: Redeker
authors.forename: Kitty M C
authors.initials: KM
authors.lastname: Kwappenberg
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: Jaap
authors.initials: J
authors.lastname: Oostendorp
authors.forename: A Rob P M
authors.initials: AR
authors.lastname: Valentijn
authors.forename: Loraine M
authors.initials: LM
authors.lastname: Fathers
authors.forename: Marij J P
authors.initials: MJ
authors.lastname: Welters
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.forename: Gemma G
authors.initials: GG
authors.lastname: Kenter
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
authors.forename: Rienk
authors.initials: R
authors.lastname: Offringa
mesh_terms: D052685:Alphapapillomavirus / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D003429:Cross Reactions / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D009856:Oncogene Proteins, Viral