Grant: Master's Award: Canada Graduate Scholarships

The cell-mediated immune response relies on cytotoxic T cells identifying cells expressing non-self proteins. Cells degrade intracellular proteins and display the resultant protein sequences (peptides) for recognition. T cell surface receptors recognize a near-infinite number of peptides, but each individual T cell is activated by a specific one. An activated T cell subsequently multiplies and kills any cells displaying that peptide. T cells which recognize self-proteins are deleted, thus mature T cells only recognize foreign proteins, typically due to viral infection, mutation, or other cellular malfunction. Tumors consist of cells that proliferate uncontrollably due to accumulative mutations. These mutations can serve as immune targets, optimal for T cell response, as they are unique to the tumor. Our lab has identified a potential target for immune recognition in ovarian cancer: Lactate Dehydrogenase C (LDHC) is often upregulated in ovarian tumors, yet absent in the female body, normally expressed only in the testis. In order to discover if T cells can recognize LDHC expression, we synthesized a library of peptides spanning the protein. T cells from three individual ovarian cancer patients were screened, and a reactive T cell clone was isolated and grown. This T cell clone was activated by a single peptide from LDHC. To characterize this response, fragments of this peptide must be used to find the shortest sequence that it will recognize. I must also determine if this peptide is naturally delivered to the cell surface and assess the cell-killing ability of the clone. Subsequent projects will aim to assess the viability of similar targets as well as push towards clinical therapy by using different methods to stimulate the immune system.