The expression and potential function of cellular prion protein in human lymphocytes.
We examined expression of the normal cellular prion protein (PrP(C)) in human peripheral blood mononuclear cells (PBMC) and in transfected neuroblastoma 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 Mabs reacted with PrP(C) expressed by human PBMC. PrP(C) is expressed at high levels in human T cells, B cells, monocytes, and dendritic cells, but not in red blood cells. Immunoblotting studies revealed that the PrP(C) glycoforms and the composition of the N-linked glycans on PrP(C) in human PBMC are different from those of the brain or the neuroblastoma cells. In human PBMC and the neuroblastoma cell lines the N-terminal portion of the PrP(C) is hypersensitive to proteolytic digestion, suggesting that the N-terminus of the PrP(C) on the surface of a living cell lacks secondary structure. We found that the level of PrP(C) expressed on the surface of human T lymphocytes was up-regulated as a consequence of cellular activation. Accordingly, memory T cells express more PrP(C) than naïve T cells. In addition, the proliferation of human T lymphocytes stimulated with an anti-CD3 Mab was inhibited by anti-PrP(C) Mabs. Collectively, these results suggest that PrP(C) can participate in signal transduction in human T lymphocytes.
Li
R
R
Institute of Pathology, Division of Neuropathology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, Cleveland, Ohio 44106-4943, USA.
Liu
D
D
Zanusso
G
G
Liu
T
T
Fayen
J D
JD
Huang
J H
JH
Petersen
R B
RB
Gambetti
P
P
Sy
M S
MS
D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002455:Cell Division; D019286:Endopeptidase K / Q000378:metabolism; D018985:Epitopes, B-Lymphocyte / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D006031:Glycosylation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D018621:PrPC Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D013601:T-Lymphocytes; D014162:Transfection; D014357:Trypsin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D018985:Epitopes, B-Lymphocyte; D018621:PrPC Proteins; D014357:Trypsin; D019286:Endopeptidase K