Chan, Siaw Li

Abstract Effective T cell function protects us from pathogens as well as cancer. However when T cell activation is dysfunctional, it has detrimental effects. If T cell activation cannot be shut down, it may cause autoimmunity. Therefore, it is crucial for us to study how T cell activation is regulated. Calcium modulating cyclophilin ligand (CAML) is a ubiquitously expressed endoplasmic reticulum protein. Using a transgenic conditional knock-out mouse model to delete CAML, we previously demonstrated that CAML is required for early embryonic development and thymopoiesis. Additionally, cells lacking CAML do not respond to EGFR stimulation due to a receptor recycling defect. However, the role of CAML in mature, peripheral T cells is not well understood. Here we provide preliminary data showing that loss of CAML in peripheral T cells leads to defective T cell activation and proliferation upon TCR stimulation, and inducing cell death through Fas ligand engagement. We hypothesize that CAML regulates components that are required to sustain optimum TCR signaling and function. T cell responsiveness to TCR stimulation is critical for T cells to deliver effector functions during antigen recognition and activation. Therefore understanding the regulation of TCR signaling by CAML will provide insight into novel mechanisms of immune regulation. These studies may provide potential treatments of immunodeficiency, autoimmunity or other inflammation associated diseases.