Prion protein is a component of the multimolecular signaling complex involved in T cell activation

In this study we analyzed the interaction of prion protein PrP(C) with components of glycosphingolipid-enriched microdomains in lymphoblastoid T cells. PrP(C) was distributed in small clusters on the plasma membrane, as revealed by immunoelectron microscopy. PrP(C) is present in microdomains, since it coimmunoprecipitates with GM3 and the raft marker GM1. A strict association between PrP(C) and Fyn was revealed by scanning confocal microscopy and coimmunoprecipitation experiments. The phosphorylation protein ZAP-70 was immunoprecipitated by anti-PrP after T cell activation. These results demonstrate that PrP(C) interacts with ZAP-70, suggesting that PrP(C) is a component of the multimolecular signaling complex within microdomains involved in T cell activation.