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 glycosylphosphatidy...

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Bibliographic Details
Published in:Biochemical journal 1993-08, Vol.293 (3), p.633-640
Main Authors: MENG-QI XIA, HALE, G, LIFELY, M. R, FERGUSON, M. A. J, CAMPBELL, D, PACKMAN, L, WALDMANN, H
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Antibodies - immunology
Antigenic determinants, haptens, artificial antigens
Antigens
Antigens, CD - chemistry
Antigens, CD - immunology
Antigens, Neoplasm
Binding Sites, Antibody
Biological and medical sciences
CD52 Antigen
Complement System Proteins - chemistry
Epitopes - chemistry
Epitopes - immunology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Glycoproteins
Glycosylphosphatidylinositols - chemistry
Glycosylphosphatidylinositols - immunology
Hydrolysis
Molecular immunology
Molecular Sequence Data
Pronase - chemistry
Protein Conformation
Sequence Homology, Amino Acid
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Summary: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.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj2930633