Cervical cancer caused by human papillomavirus (HPV) is one of the leading causes of morbidity and mortality among women worldwide. The virus infects basal keratinocyte and persistent high-risk HPV infection along with an elevated level of E6 and E7 oncoproteins associates with malignancy. As a model of HPV-mediated precancers, we have utilized K14E7 transgenic mice which express HPV16 E7 oncoprotein in keratinocytes and as a result of that display epithelial hyperplasia and suppressed local immune responses. To assess the effect of HPV16 E7 expressing skin on DC activation and function, we characterized DC surface molecule expression and MHC-II-restricted antigen presentation. As measured by flow cytometry, DCs from the epidermis and skin draining lymph nodes of K14E7 mice have significantly increased levels of CD80 and CD86 expression but reduced MHC-II expression relative to C57BL/6 mice. In contrast, skin DCs from K14E7 mice deficient in lymphocytes (Rag1-/- x K14E7) contain high levels of costimulatory and MHC-II molecules. After intradermal OVA immunization of K14E7 mice, CD4 T cell priming is impaired compared to non-transgenic mice.  Therefore, the data suggest that lymphocytes within K14E7 mice impair the expression of MHC-II on DCs with an associated reduction in CD4 T cell function.  This may have implications for the generation of CD4 T cell help in HPV-mediated cancers.