Memory T-Cells Specific for Novel HPV 16 E6 Epitopes in Women Whose HPV 16 Infection Has Become Undetectable

Departments of Pathology, and Microbiology and Immunology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Microbiology and Parasitology, College of Basic Medical Sciences, China Medical University, Shenyang, China; Department of Pediatrics, College of Medicine, University of California at San Francisco

^* To whom correspondence should be addressed. Email: xwang4{at}uams.edu.

	Abstract

Human papillomavirus (HPV)-specific T-cell response to the human papillomavius type 16 (HPV 16) E6 protein has been shown to be associated with successful viral clearance. The patterns of CD8 T-cell epitopes within human papillomavius type 16 (HPV 16) E6 protein were previously studied in two women with HPV 16 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. ELISPOT and tetramer analyses were performed on peripheral blood mononuclear cells (PBMCs) 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 HPV 16 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.