The expression and potential function of cellular prion protein in human lymphocytes

We examined expression of the normal cellular prion protein (PrPC) in human peripheral blood mono-nuclear cells (PBMC) and in transfected neuroblastom a cells with a panel of six monoclonal antibodies (Mabs). While all six of the Mabs reacted strongly with the neuroblastoma cells, only four of the Ma bs reacted with PrPC expressed by human PBMC, PrPC is expressed at high lev els in human T cells, B cells, monocytes, and dendritic cells, but not in r ed blood cells. Immunoblotting studies revealed that the PrPC glyco-forms a nd the composition of the N-linked glycans on PrPC in human PBMC are differ ent from those of the brain or the neuroblastoma cells. In human PBMC and t he neuroblastoma cell lines the N-terminal portion of the PrPC is hypersens itive to proteolytic digestion, suggesting that the N-terminus of the PrPC on the surface of a living cell lacks secondary structure. We found that th e level of PrPC expressed on the surface of human T lymphocytes was up-regu lated as a consequence of cellular activation. Accordingly, memory T cells express more PrPC than naive T cells. In addition, the proliferation of hum an T lymphocytes stimulated with an anti-CDS Mab was inhibited by anti-PrPC Mabs, Collectively, these results suggest that PrPC can participate in sig nal transduction in human T lymphocytes, (C) 2001 Academic Press.