Antigen specific T cell activation is an important step in the establishment of adaptive immunity. It is well established that cytoskeletal reorganization plays a pivotal role during T cell activation. It functions by facilitating the aggregation of T cell receptor, signaling molecules and accessory molecules into an organized super molecular activation cluster, thus providing sustained signaling required for T cell activation. However, the molecular pathways that mediates the cytoskeletal changes upon T cell stimulation is poorly understood. Ras related Rho family GTPases have been implicated to mediate cytoskeletal changes upon various stimuli, including T cell stimulation. Rac2 is one member of Rho family GTPases and we have observed increased Rac2 expression during T cell activation and differentiation. Thus, it is speculated that Rac2 might playa role in T cell activation and differentiation. To test this hypothesis, I have generated a conditional Rac2 knockout (RaC2K0) mouse to allow assessment of functional changes in mature T cells. Preliminary experiments have shown that T cells from the Rac2K0 mice showed decreased proliferation upon antigen stimulation. In this proposal, I present plans to study cytoskeletal reorganization upon T cell stimulation, cell cycle progression, mitogen activated kinase activation in Rac2 deficient T cells. Rac2 function will be further assessed in T cell dependent immune responses using T cell specific Rac2 deficient mice. This work should provide new information about this T cell activation pathway and will also be valuable in the assessment of Rac2 as a therapeutic target for T cell regulation.
