HETEROMULTIMERIC COMPLEXES OF CD40 LIGAND ARE PRESENT ON THE CELL-SURFACE OF HUMAN T-LYMPHOCYTES

CD40 ligand (CD40L), a 33-kDa type II membrane glycoprotein expressed primarily on activated CD4(+) T lymphocytes, is responsible for the he lper function of T cells on resting B cells in a non-antigen dependent , non-major histocompatability complex-restricted fashion, Interaction of CD40L with its receptor CD40 induces proliferation of and isotype switching in B lymphocytes. Recently we solved the x-ray structure of recombinant soluble CD40L and showed that, similar to other members of the tumor necrosis factor family, CD40L indeed exists as a trimer. We now report that, under normal physiological conditions, CD40L molecul es exist as heteromultimeric complexes. These CD40L complexes, made of the full length and smaller fragments of CD40L, are present on the ce ll surface of T lymphocytes and are capable of interacting with CD40 m olecule, A prominent fragment with a mass of 31 kDa accounts for as mu ch as half of the CD40L on the surface of Jurkat cells. N-terminal seq uence data revealed that this fragment lacks the cytoplasmic tail. A m inor 18-kDa fragment of CD40L was also characterized which lacks the c ytoplasmic tail, transmembrane region, and stalk region of the extrace llular domain. The presence of CD40L heteromultimeric variants implies an additional regulation of the functional activity of this ligand co mplex.