Cell-mediated immune responses to the human papillomavirus type 16 (HPV 16) E6
protein have been shown to be important in viral clearance and in regression of cervical lesions. Here, detailed analyses of a novel HPV 16 E6 CD4
T-cell epitope from a subject with
cervical intraepithelial neoplasia 1 are described. This subject had demonstrated HPV 16 CD4 T-cell responses to multiple regions within the E6
protein. Isolation and cloning of CD4 T-cells were performed by magnetic selection of
interferon-γ secreting cells and limiting dilution. A single HPV 16-specific T-cell clone isolated was shown to have a specificity to HPV 16 E6 52-62 restricted by the
HLA-DR11 molecule. Homologous sequences (≥70%
amino acid homology) were identified for HPV types 31, 33, 45, 58, 73, but cross-recognition was demonstrated only for HPV 45. Based on work performed by our group and others, it is known that this short
peptide contains multiple CD4 and CD8 T-cell HPV
epitopes and would be an ideal region to incorporate into a design of
vaccines and
immunotherapies against HPV-associated
malignancies.