Investigating Cellular Immunity Using the SV40 Large Tumor Antigen

The Simian Virus 40 Large Tumor antigen (SV40 T ag) is a viral oncoprotein that is capable of inducing tumors and serving as the target for anti-tumor T cell responses. Because of this, the SV40 T ag has been studied extensively as a model to better understand immune control of solid tumors. Our laboratory has recently identified three CD4+ epitopes within the T ag and is conducting studies to characterize their role(s) in regulating cellular immunity to the SV40 T ag. Towards this goal, we have generated a cell line (C2a) that expresses a derivative of the T ag in which the three newly discovered CD4+ epitopes have been inactivated by substitution or deletion. The induction of SV40 T ag specific CD8+ memory T cells was investigated using C2a cells which had been grown in serum-free HL-1 media. The role of CD4+ T cells in the negative regulation of the immune response to SV40 T ag was also investigated. A new search was conducted to find additional new CD4+ epitopes that induce the secretion of the cytokine Interleukin-10 (IL-10). The identity of the IL-10-secreting cells was also investigated by ICS. While no new epitopes were uncovered, T cells responding to the known CD4+ epitopes were shown to secrete IL-10, indicating that they may play a role in negative regulation