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[Cancer Research 62, 472-479, January 15, 2002]
© 2002 American Association for Cancer Research

Immunology

Frequent Detection of Human Papillomavirus 16 E2-specific T-helper Immunity in Healthy Subjects1

Annemieke de Jong2, Sjoerd H. van der Burg2,,3, Kitty M. C. Kwappenberg, Jeanette M. van der Hulst, Kees L. M. C. Franken, Annemieke Geluk, Krista E. van Meijgaarden, Jan Wouter Drijfhout, Gemma Kenter, Pieter Vermeij, Cornelis J. M. Melief and Rienk Offringa

Departments of Immunohematology and Blood Transfusion [A. d. J., S. H. v. d. B., K. M. C. K., J. M. v. d. H., K. L. M. C. F., A. G., K. E. v. M., J. W. D., C. J. M. M., R. O.], Gynecology [G. K.], and Clinical Pharmacy and Toxicology [A. d. J., P. V.], Leiden University Medical Center, 2300 RC Leiden, the Netherlands

The incidence of genital human papillomavirus (HPV) infections is high in young, sexually active individuals. Most infections are cleared within 1 year after infection. The targets for the cellular immune response in this process of viral clearance remain to be identified, but the expression pattern of the E2 protein in early infection and low-grade cervical intraepithelial neoplasia renders this early protein a candidate antigen. Therefore, we studied the HPV16 E2-specific T-cell responses in more detail. Very strong proliferative responses against one or more peptide-epitopes derived from this antigen can be found in peripheral blood mononuclear cell cultures of approximately half of the healthy donors. Additional analysis revealed that at least a majority of these responses represent reactivity by memory CD4+ T-helper (Th) 1-type cells capable of secreting IFN-{gamma} on antigenic stimulation. Interestingly, all of the E2 peptides against which strong responses were detected are clustered in the key functional domains of the E2 protein, which are conserved to considerable extent between HPV types. This suggests that HPV16 E2-specific Th memory may be installed through encounter with HPV types other than HPV16. Indeed, one HPV16 E2-specific Th clone was found to cross-react against homologuous peptides from other HPV types, but three other Th clones failed to show similar cross-reactivity. Therefore, part of the HPV16 E2-specific Th memory may relate to previous encounter of other HPV types, whereas the majority of the immune repertoire concerned is most likely established through infection with HPV16 itself. Our data are the first to reveal that the T-cell repertoire of healthy donors can contain particularly high frequencies of E2-specific memory Th cells and suggest that boosting of this immunity can be used for preventive and therapeutic vaccination against HPV-induced lesions.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2002 by the American Association for Cancer Research.