title: Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis.
abstract: 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.
authors.affiliation: Department of Pathology, University of Cambridge, U.K.
authors.forename: M Q
authors.initials: MQ
authors.lastname: Xia
authors.forename: G
authors.initials: G
authors.lastname: Hale
authors.forename: M R
authors.initials: MR
authors.lastname: Lifely
authors.forename: M A
authors.initials: MA
authors.lastname: Ferguson
authors.forename: D
authors.initials: D
authors.lastname: Campbell
authors.forename: L
authors.initials: L
authors.lastname: Packman
authors.forename: H
authors.initials: H
authors.lastname: Waldmann
mesh_terms: 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
chemical_list: 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