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Clinical and Vaccine Immunology, June 2008, p. 937-945, Vol. 15, No. 6
1071-412X/08/$08.00+0     doi:10.1128/CVI.00404-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Memory T Cells Specific for Novel Human Papillomavirus Type 16 (HPV16) E6 Epitopes in Women Whose HPV16 Infection Has Become Undetectable{triangledown}

Xuelian Wang,1,2* Anna-Barbara Moscicki,3 Laura Tsang,4 Andrea Brockman,4 and Mayumi Nakagawa1

Departments of Pathology,1 Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas,4 Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China,2 Department of Pediatrics, College of Medicine, University of California at San Francisco, San Francisco, California3

Received 5 October 2007/ Returned for modification 9 January 2008/ Accepted 14 April 2008

Human papillomavirus (HPV)-specific T-cell response to the HPV type 16 (HPV16) E6 protein has been shown to be associated with successful viral clearance. The patterns of CD8 T-cell epitopes within HPV16 E6 protein were previously studied in two women with HPV16 clearance. The goal of this study was to characterize these epitopes in terms of their minimal and optimal amino acid sequences and the human leukocyte antigen (HLA) restriction molecules. The presence of the epitope-specific memory T cells after viral clearance was also examined. In subject A, the dominant epitope was characterized to be E6 75-83 (KFYSKISEY), restricted by the HLA-B62 molecule, while that of subject B was E6 133-142 (HNIRGRWTGR), restricted by the HLA-A6801 molecule. Homologous epitopes were identified in five other high-risk HPV types for both of these epitopes, but they were not recognized by respective T-cell clone cells. An enzyme-linked immunospot assay or tetramer analysis was performed on peripheral blood mononuclear cells from blood samples collected after viral clearance but prior to isolation of the T-cell clones. The presence of epitope-specific memory T cells was demonstrated. These data suggest that HPV-specific memory T cells were generated in vivo and that they may remain in circulation many months, if not years, after viral clearance. Our findings broaden the spectrum of the CD8 T-cell epitopes of the HPV16 E6 protein. The characterization of novel T-cell epitopes and long-lasting epitope-specific memory T cells may be useful for the development of a potential epitope-based vaccine.

* Corresponding author. Mailing address: Department of Pathology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 824, Little Rock, AR 72205. Phone: (501) 526-7812. Fax: (501) 526-5934. E-mail: xwang4{at}uams.edu

{triangledown} Published ahead of print on 30 April 2008.

Clinical and Vaccine Immunology, June 2008, p. 937-945, Vol. 15, No. 6
1071-412X/08/$08.00+0     doi:10.1128/CVI.00404-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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