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 helper 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 molecules exist as heteromultimeric complexes. These CD40L complexes, made of the full length and smaller fragments of CD40L, are present on the cell surface of T lymphocytes and are capable of interacting with CD40 molecule. A prominent fragment with a mass of 31 kDa accounts for as much as half of the CD40L on the surface of Jurkat cells. N-terminal sequence data revealed that this fragment lacks the cytoplasmic tail. A minor 18-kDa fragment of CD40L was also characterized which lacks the cytoplasmic tail, transmembrane region, and stalk region of the extracellular domain. The presence of CD40L heteromultimeric variants implies an additional regulation of the functional activity of this ligand complex.
Hsu
Y M
YM
Department of Protein Engineering, Biogen Inc., Cambridge, Massachusetts 02142, USA. yen-ming_hsu@biogen.com
Lucci
J
J
Su
L
L
Ehrenfels
B
B
Garber
E
E
Thomas
D
D
D000945:Antigens, Differentiation, T-Lymphocyte / Q000737:chemistry*; D019013:CD40 Antigens / Q000737:chemistry*; D023201:CD40 Ligand; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry; D012697:Serine Endopeptidases / Q000378:metabolism; D013601:T-Lymphocytes / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry*
D000945:Antigens, Differentiation, T-Lymphocyte; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D012697:Serine Endopeptidases; C028344:glutamyl endopeptidase