A soluble form of TRAP (CD40 ligand) is rapidly released after T cell activation.
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.
Graf
D
D
Robert Koch-Institute, Berlin, Germany.
Müller
S
S
Korthäuer
U
U
van Kooten
C
C
Weise
C
C
Kroczek
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D023201:CD40 Ligand; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand