Phosphorylcholine acts as a Ca2+-dependent receptor molecule for lymphocyte perforin.
Large granular lymphocytes and cytolytic T-lymphocytes (CTL) contain numerous cytoplasmic granules thought to be responsible, at least in part, for the cytolytic activity of these effector cells. Isolated granules are lytic for a variety of target cells and the granule proteins are specifically released upon target-cell interaction. Major proteins in mouse CTL granules are a family of seven serine proteases designated granzymes A to G, and a pore-forming protein called perforin (cytolysin). Purified perforin is cytolytic in the presence of Ca2+ and shows ultrastructural, immunological and amino-acid sequence similarities to complement component C9. Despite these similarities, perforin and C9 are clearly distinct in their mode of target-cell recognition. Whereas C9 insertion is absolutely dependent on a receptor moiety assembled from the complement proteins C5b, C6, C7, and C8 on the target-cell membrane, no requirement for a receptor molecule has been reported for perforin. Here, we demonstrate that phosphorylcholine acts as a specific, Ca2+-dependent receptor molecule for perforin.
Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
J
J
Tschopp
S
S
Schäfer
D
D
Masson
M C
MC
Peitsch
C
C
Heusser
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives*; D002846:Chromatography, Affinity; D004912:Erythrocytes / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism*; D054353:Perforin; D010743:Phospholipids / Q000494:pharmacology; D010767:Phosphorylcholine / Q000378:metabolism* / Q000494:pharmacology; D052899:Pore Forming Cytotoxic Proteins; D011485:Protein Binding; D012756:Sheep; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010743:Phospholipids; D052899:Pore Forming Cytotoxic Proteins; D010767:Phosphorylcholine; D054353:Perforin; D002794:Choline; D002118:Calcium