Human papillomavirus (HPV)
infection, particularly type 16, is causally associated with the development of
cervical cancer. The E6 and E7
proteins of HPV are constitutively expressed in cervical
carcinoma cells making them attractive targets for CTL-based
immunotherapy. However, few studies have addressed whether cervical
carcinomas can process and present HPV E6/E7-derived Ags for recognition by CTL. We generated
HLA-A*0201-restricted CTL clones against HPV16 E6(29-38) that recognized HPV16 E6 Ags transfected into B lymphoblastoid cells. These CTL were unable to recognize
HLA-A*0201(+) HPV16 E6(+) cervical
carcinoma cell lines even when the level of endogenous HPV16 E6 in these cells was increased by transfection. This defect in presentation of HPV16 E6(29-38) correlated with low level expression of HLA class I,
proteasome subunits low molecular mass
protein 2 and 7, and the transporter
proteins TAP1 and TAP2 in the cervical
carcinoma cell lines. The expression of all of these
proteins could be up-regulated by IFN-gamma, but this was insufficient for CTL recognition unless the level of HPV16 E6 Ag was also increased by transfection. CTL recognition of the HPV16 E6(29-38)
epitope in 721.174 B cells was dependent on TAP expression but independent of immunoproteasome expression. Collectively, these findings suggest that presentation of the HPV16 E6(29-38)
epitope in cervical
carcinoma cell lines is limited both by the level of TAP expression and by the low level or availability of the source HPV E6
oncoprotein. These observations place constraints on the use of this, and potentially other, HPV-derived CTL
epitopes for the
immunotherapy of
cervical cancer.