T-cell responses to oncogenic merkel cell polyomavirus proteins distinguish patients with merkel cell carcinoma from healthy donors.

Publication Type:

Journal Article

Source:

Clinical cancer research : an official journal of the American Association for Cancer Research, Volume 20, Issue 7, p.1768-78 (2014)

Keywords:

2014, Center-Authored Paper, Clinical Research Division, Experimental Histopathology Core Facility, Immune Monitoring Core Facility, May 2014, Specimen Processing Core Facility

Abstract:

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with strong evidence of viral carcinogenesis. The association of MCC with the Merkel cell polyomavirus (MCPyV) may explain the explicit immunogenicity of MCC. Indeed, MCPyV-encoded proteins are likely targets for cytotoxic immune responses to MCC as they are both foreign to the host and necessary to maintain the oncogenic phenotype. However, to date only a single MCPyV-derived CD8 T-cell epitope has been described, thus impeding specific monitoring of T-cell responses to MCC. Method: To overcome this limitation, we scanned the MCPyV oncoprotein large T and small T antigens and the virus capsid protein VP1 for potential T-cell epitopes, and tested for MHC class I affinity. We confirmed the relevance of these epitopes using a high-throughput platform for T-cell enrichment and combinatorial encoding of MHC class I multimers.