A cell-binding Arg-Gly-Asp sequence is present in close proximity to the major linear antigenic region of HCV NS3.
By sequence analysis of the HCV NS3 protein we identified an Arg-Gly-Asp (RGD) motif, which is a known sequence for integrin-mediated cell adhesion, within a region of high hydrophilicity and surface probability. We therefore probed the complete NS3 protein for antigenic regions and cell binding activities using synthetic peptides. Antigenic regions were located to residues 1007-1022, 1047-1062, 1127-1142 and 1207-1232. The RGD-sequence reside two residues apart from the antigenic region at residues 1127-1142. Cell-adhesion experiments showed that NS3 peptides containing the RGD-sequence bound HUT-78 T-cells in a dose dependent manner. Antibodies to region 1127-1142 were found in all categories of HCV patients, arguing against the clinical significance of these antibodies. Extracellular NS3 proteins might disturb the migration of immune cells to the infected area by blocking the RGD-binding integrins, and thus, protect the infected cells.
Zhang
Z X
ZX
Department of Immunology, Microbiology, Pathology, and Infectious Diseases, Karolinska Institutet, Huddinge University Hospital, Sweden.
Sönnerborg
A
A
Sällberg
M
M
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000737:chemistry*; D001665:Binding Sites; D002448:Cell Adhesion; D002460:Cell Line; D016174:Hepacivirus / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
D000956:Antigens, Viral; D009842:Oligopeptides; D017361:Viral Nonstructural Proteins; C047981:arginyl-glycyl-aspartic acid