Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis.
CAMPATH-1 antibodies recognize a unique molecule on human lymphocytes and are unusually efficient at causing cell lysis with homologous complement. They have been successfully used for lymphocyte depletion in vivo in a variety of diseases. We find that the antigen is a very small glycosylphosphatidylinositol (GPI)-anchored glycoprotein with a mature peptide comprising only 12 amino acids. It can be separated into two distinct antigenic fractions which differ in their susceptibility to phosphatidylinositol-specific phospholipase C. There is one N-linked glycosylation site, but no evidence for O-glycosylation despite the presence of several serine and threonine residues. The antibodies were found to bind, albeit with a generally reduced affinity, to a proteolytic fragment containing the C-terminal tripeptide and the GPI anchor. We postulate that one of the reasons why the CAMPATH-1 antibodies are so good for cell lysis is because they bind to an epitope which is likely to be very close to the lipid bilayer.
Xia
M Q
MQ
Department of Pathology, University of Cambridge, U.K.
Hale
G
G
Lifely
M R
MR
Ferguson
M A
MA
Campbell
D
D
Packman
L
L
Waldmann
H
H
D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000737:chemistry* / Q000276:immunology; D000951:Antigens, Neoplasm; D001666:Binding Sites, Antibody; D000074301:CD52 Antigen; D003165:Complement System Proteins / Q000737:chemistry*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006023:Glycoproteins; D017261:Glycosylphosphatidylinositols / Q000737:chemistry* / Q000276:immunology; D006868:Hydrolysis; D008969:Molecular Sequence Data; D011402:Pronase / Q000737:chemistry; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D000906:Antibodies; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D000939:Epitopes; D006023:Glycoproteins; D017261:Glycosylphosphatidylinositols; D003165:Complement System Proteins; D011402:Pronase