Cellular isoform of the scrapie agent protein participates in lymphocyte activation

The scrapie agent protein (Sp33–37 or PrP Sc ) is the disease-associated isoform of a normal cellular membrane protein (Cp33–37 or PrP C ) of unknown function. We report than normal human lymphocytes and lymphoid cell lines, but not erythrocytes or granulocytes, express PrP C mRNA and protein. PrP C is detectable on the surface of lymphocytes; the surface immunoreactivity is sensitive to phosphatidylinositol-specific phospholipase C, indicating glycosyl-phosphatidylinositol membrane anchorage. Lymphocyte PrP C surface abundance is increased by cell activation, and polyclonal antibodies to PrP C suppress mitogen-induced activation. We conclude that PrP C is a lymphocyte surface molecule that may participate in cell activation.