LPS-binding protein and CD14-dependent attachment of hepatitis B surface antigen to monocytes is determined by the phospholipid moiety of the particles.
It was observed recently that recombinant yeast-derived hepatitis B surface antigen (rHBsAg) particles, which contain the S protein only, bind almost exclusively to monocytes. It is shown here that binding requires the presence of the LPS receptor CD14. Furthermore, evidence is presented that a domain on CD14 that is identical to or largely overlaps with the LPS-binding pocket is instrumental for the attachment of rHBsAg. Additionally, it is shown that the heat-labile LPS-binding protein (LBP) catalyses the binding of rHBsAg to the cells. Remarkably, natural plasma-derived HBsAg (pHBsAg) does not have this property. pHBsAg devoid of its lipids and reconstituted with phosphatidylserine or phosphatidylglycerol acquires the characteristic of yeast-derived HBsAg. Clearly, the interaction of rHBsAg with the cell membrane is determined by the presence of charged phospholipids that are absent in pHBsAg. Although a lipid-receptor interaction is suggested, antibody-inhibition experiments suggest a possible involvement of the C-terminal region of the S protein in the interaction with monocytes. The possible implications of these observations for hepatitis B virus (HBV) infection and HBV vaccine efficiency are discussed.
Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium1.
Peter
P
Vanlandschoot
Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium1.
Freya
F
Van Houtte
Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium1.
Annelies
A
Roobrouck
Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium1.
Ali
A
Farhoudi
Institute of Immunology and Transfusion Medicine, Ernst Moritz Arndt University, Greifswald, Germany2.
Felix
F
Stelter
Department of Biochemistry and Molecular Biophysics, Virginia Commonwealth University, Richmond, VA, USA3.
Darell L
DL
Peterson
Departamento de Bioquimica y Biologia Molecular, Universidad Complutense, Madrid, Spain4.
Julian
J
Gomez-Gutierrez
Departamento de Bioquimica y Biologia Molecular, Universidad Complutense, Madrid, Spain4.
Francisco
F
Gavilanes
Center for Vaccinology, Department of Clinical Biology, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium1.
Geert
G
Leroux-Roels
D000209:Acute-Phase Proteins; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D006224:Cricetinae; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins; D009000:Monocytes / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D006514:Hepatitis B Surface Antigens; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D010743:Phospholipids; D011994:Recombinant Proteins; D000099231:Lipopolysaccharide-Binding Protein