Prion protein resides in membrane microclusters of the immunological synapse during lymphocyte activation.

Expression of prion protein (PrP) has been reported for a variety of cell types including neuronal cells, haematopoietic stem cells, antigen-presenting cells, as well as lymphocytes. However, besides this widespread occurrence little is known about the physiological roles exhibited by this enigmatic protein. In this study, the contribution of PrP to the classical T-lymphocyte activation process was characterized by clustering the T-cell receptor component CD3epsilon as well as PrP with soluble and surface-immobilized antibodies, respectively. We present evidence that PrP is a component of signaling structures recently described as plasma membrane microclusters established during T-lymphocyte activation. The formation of immunological synapses, however, did not depend on the presence of PrP as proven by siRNA knockdown experiments, indicating very subtle physiological roles of PrP in vivo within the immune system.