Jesusa Capera-Aragones, PhD, Postdoctoral Fellow University of Oxford T lymphocytes patrol in our body continuously scanning for specific pathogens or cancerous cells. If an infected or malignant cell is detected, specific T lymphocytes will activate and coordinate a complex immune response that will efficiently clear the undesired cells. However, the process of antigen recognition must be tightly regulated to avoid undesired autoimmune reactions to healthy cells. Thus, T lymphocytes will only initiate a response if the combination of different chemical, mechanical, and electrical signals surpasses a certain threshold required for their activation. Such threshold is controlled by electrochemical waves of calcium happening during the immunological synapse. Therefore, understanding the mechanisms controlling calcium movements is crucial to understand and modulate the process of T lymphocyte activation. However, little is known about the bioelectrical control of the immune response. Dr. Capera-Aragones hypothesizes that different cation currents are strategically organized at the synapse to optimally control calcium waves and ultimately lead to activation. Thus, she will apply state-of-the-art microscopy to visualize and quantitatively analyse the distribution of relevant ion channels at the immunological synapse. In addition, she will study the role of ion channels on processes such as anergy and exhaustion, with relevance to cancer and autoimmunity. These cells are resistant to activation and she will study the causal relationship between the non-responsive state and a possible disarrangement of the currents at the synapse. Finally, she will explore the therapeutic potential of ion channels expressed in extracellular vesicles released by activated T lymphocytes. Projects and Grants At the onset of T cell activation: Ion channels and the immune synapse University of Oxford | All Cancers | 2022 | Michael L. Dustin, Ph.D.
