Noble, Peter Richard; (1999) CD4 T lymphocyte responses to human papillomavirus type 16. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Human papillomavirus type 16 (HPV16) is the commonest of the oncogenic papillomaviruses and is the main cause of two thirds of cervical carcinoma worldwide. There is good reason to believe that HPV infection is controlled by a cellular immune response. The demonstration and characterisation of human CD4 positive T lymphocytes primed by HPV 16 would be very useful for the development and evaluation of vaccines to prevent or attenuate HPV 16 infection. To date it has not proved possible to detect such lymphocytes using conventional means. A novel and simple method is described of detecting antigen-specific primed CD4 T cells in the peripheral blood. This has been used to detect cells primed to HPV 16 and to influenza nucleoprotein but could be used to detect responses to other antigens. Using this method, responses to HPV 16 have been detected in three women with documented CIN (these responses were chiefly to E6 and E7) and in two young uncharacterised control individuals (to L1 alone). In three individuals it was possible to repeat the assays and the responses were found to be transient. Using a completely different approach, evidence is presented that DNA immunisation in the hind legs of mice generates a response specific for HPV 16 L1 in the para aortic lymph nodes and that cells taken from these nodes can be restimulated in vitro by HPV 16 L1 protein. A set of overlapping 25mer peptides representing HPV16 E7 and L1 could not restimulate human or murine responses although at least two of them were immunogenic in mice. Reasons for this are discussed.

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