Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol-anchored glycoprotein which is an exceptionally good target for complement lysis

Meng-Qi Xia, Geoffrey Hale, M. Robert Lifely, Michael A. J. Ferguson, D Campbell, Len Packman, Herman Waldmann

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    177 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)633-640
    Number of pages8
    JournalBiochemical Journal
    Volume293 ( Pt 3)
    Publication statusPublished - 1993

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