A soluble form of TRAP (CD40 ligand) is rapidly released after T cell activation

Eur J Immunol. 1995 Jun;25(6):1749-54. doi: 10.1002/eji.1830250639.

Abstract

TRAP is a tumor necrosis factor (TNF)-related, 33-kDa type II transmembrane protein almost exclusively expressed on the surface of activated CD4+ T lymphocytes. Interaction of TRAP with CD40 on B cells is of paramount importance for immunoglobulin class switching and subsequent synthesis of IgG, IgA or IgE in vivo. We now provide evidence that activated T cells not only express cell membrane-associated TRAP but also a soluble form of TRAP (sTRAP). After generating monoclonal antibodies against TRAP and establishing a TRAP-specific enzyme-linked immunosorbent assay we were able to detect substantial amounts of sTRAP in the supernatants of activated T cells. The onset and rate of sTRAP release was found to parallel the expression of TRAP on the cell surface. sTRAP, an 18-kDa protein, is generated by proteolytic processing of full-length TRAP in an intracellular compartment. Starting with methionine 113 of full-length TRAP, sTRAP lacks the transmembrane region and a part of the extracellular domain but contains the entire TNF-alpha homology region and can, therefore, bind to CD40. Like other members of the TNF superfamily (e.g. TNF-alpha, Fas/APO-1 ligand), TRAP thus has the potential to be biologically active not only in a transmembrane form but also as a soluble molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • CD40 Ligand
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Ligands
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Monoclonal
  • Ligands
  • Membrane Glycoproteins
  • CD40 Ligand