Cell Surface ADP-Ribosyltransferase Regulates Lymphocyte Function-Associated Molecule-1 (LFA-1) Function in T Cells

Eiji Nemoto, Yajing Yu, Gunther Dennert

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)

Abstract

Post-translational modifications are important in regulating the functions of signal proteins. This is well established for intracellular proteins, but little is known in the case of extracellular domains of cell surface molecules. We recently described a cell surface protein, mono-ADP-ribosyltransferase (ADPRT), on cytotoxic T cells and showed that it mediates attachment of ADP-ribose to cell surface proteins. Concomitantly, cytolytic activity and cell proliferation are inhibited. Here we report that one of the principal proteins modified by this enzyme is lymphocyte function-associated molecule-1 (LFA-1). While both chains are ADP-ribosylated on the extracellular domain of the molecule, persistence of the modification differs between the chains. Label is released from the β-chain by 1 h, yet remains for at least 6 h on the α-chain. Loss of label is suppressed by phosphodiesterase inhibitors such as ADP-ribose and p-nitrophenylthymidine 5′-monophosphate, pointing to the involvement of this class of enzyme. Modification of LFA-1 requires expression of the cell surface ADPRT and causes the loss of epitopes recognized by α-and β-chain-specific Abs. Concomitantly, the generation of inositol phosphates induced by Ab cross-linking of LFA-1 is significantly inhibited. Consistent with this effect, anti-LFA-1-induced homotypic cell adhesion is also inhibited. These effects are not seen in cells from which the ADPRT was removed by phospholipase C. Moreover, cells lacking the cell surface ADPRT are not inhibited by NAD in the cell adhesion assay, but gain this property upon transfection with the ADPRT gene. It is concluded that the cell surface protein mono-ADPRT regulates LFA-1 functions.

Original languageEnglish
Pages (from-to)3341-3349
Number of pages9
JournalJournal of Immunology
Volume157
Issue number8
Publication statusPublished - 1996 Oct 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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