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

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 proccessing of full‐length TRAP in an intracellular compartment. Starting with methionine 113 of fulllength TRAP, sTRAP lacks the transmembrane region and a part of the extracellular domain but contains the entire TNF‐α homology region and can, therefore, bind to CD40. Like other members of the TNF superfamily (e.g. TNF‐α, 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.