The role of co-signalling receptors in cytotoxic lymphocyte activity during infection and cancer

Cytotoxic lymphocytes (CD8+ T and natural killer (NK) cells) are integral for immune protection against infection and in the immunosurveillance of cancer. The activation of T cells, and the cytotoxic activity of T and NK cells, relies on the formation of an immunological synapse with antigen-presenting cells, or target cells, respectively. During synapse formation, T and NK cell activation and function is fine-tuned by a range of co-signalling molecules that positively or negatively modulate lymphocyte activity. Two important receptors in the regulation of T and NK cell function are the co-signalling molecules, DNAM-1 and CD96. We have evidence that tumour cells, such as acute myeloid leukemic (AML) cells, down-regulate the expression of ligands recognised by DNAM-1 and CD96 as an immune evasion mechanism.

Preliminary data show that DNAM-1 is necessary for cytotoxic lymphocyte adhesion and synapse formation during target cell killing. This project will investigate the role of both DNAM-1 and CD96 in T cell responses to antigen, and in T and NK cell cytotoxic activity. We will also investigate the consequences of ligand expression on DNAM-1 and CD96 on NK recognition and killing of AML cells.

The aims of this project will be to:
(1) Investigate the role of DNAM-1 and CD96 in immunological synapse formation and tumour cell killing in vitro
(2) Examine the anti-tumour response in CD96 deficient mice

Techniques commonly used in this laboratory include:Tissue culture, flow cytometry, cell sorting, fixed and time-lapse confocal microscopy, cytokine assays, killing assays, real-time PCR, western blotting, mouse experimentation and general immunological techniques.

In the Oliaro laboratory, researchers investigate the regulation of cytotoxic lymphocytes – the immune cells that are responsible for the recognition and killing of cancer cells. Our research focuses on investigating immune cell interactions with cancer cells, with a particular focus on immune synapse formation.