Investigating T cell immunity against the oncogenic Merkel cell polyomavirus

Pallan, Lalit (2017). Investigating T cell immunity against the oncogenic Merkel cell polyomavirus. University of Birmingham. Ph.D.

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Abstract

Merkel cell polyomavirus (MCV) is a causative factor in Merkel cell cancer (MCC). This aggressive skin maligrancy is associated with UV-light exposure, ageing or immunosuppression, implying immune constraint of MCC development. We examined immune control over MCV in MCC patients by comparing immune parameters with donor groups who share risk factors alongside healthy controls. This showed MCC patients had frequent and strong MCV antibody responses but no differences in responses to other polyomaviruses suggesting no general defect in humoral immunity to these viruses. MCC patients had lower frequencies of B-cells while T-cells from patients with active disease proliferated relatively poorly. Quantifying peripheral T-cell responses to the large- and small T-antigens in patient groups and healthy donors by ELISpot showed that like with other polyomaviruses, responses were weak. Novel epitopes were identified by establishing T antigenipecific CD4 and CD8 T-cell clones from healthy donors which recognised antigen expressing cells. However MCC tumours and lines were found to have low levels of surface HLA Class I and Class II and could poorly process and present epitope to T-cells. Consistent with this, preliminary experiments showed that small-T inhibited epitope presentation suggesting that small-T function must be inhibited for efficient T cell targeting of infected cells.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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