title: Soluble CD30 binds to CD153 with high affinity and blocks transmembrane signaling by CD30.
abstract: CD30 is an unusual member of the TNF receptor superfamily with a duplicated segment within its extracellular domain that may function as an additional ligand binding site. The extracellular domain of CD30 is shed from cells and soluble CD30 levels are elevated in certain disease states. Soluble CD30 may bind to its ligand, CD153, with high affinity and block its interaction with membrane-bound CD30. We have generated soluble recombinant forms of CD30 and CD153 in order to characterize their interaction and assess their biological activity. Soluble trimeric CD153 bound to membrane-anchored CD30 with a relatively high affinity (K(D)=23 nM) and was effective in triggering cell death and TNF-alpha production in the presence of cross-linking antibodies. The affinity and kinetics of the interaction between soluble CD30 and CD153 were determined using the BIAcore biosensor. In contrast to other members of the TNF receptor superfamily, soluble monomeric CD30 bound to its ligand with high affinity (K(D)=4.5 nM) and prevented the interaction of cellular CD153 with immobilized CD30. Furthermore, soluble CD30 blocked cell death signals generated by cell surface-expressed CD30 effectively. These data suggest that soluble CD30 may have biological functions in vivo.
authors.affiliation: Tenovus Research Laboratory, Cancer Sciences Division, The School of Medicine, University of Southampton, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Hargreaves
authors.forename: Aymen
authors.initials: A
authors.lastname: Al-Shamkhani
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D053285:CD30 Ligand; D015704:CD4 Antigens / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D019556:COS Cells; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D006224:Cricetinae; D006801:Humans; D017730:Ki-1 Antigen / Q000096:biosynthesis / Q000378:metabolism*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012995:Solubility
chemical_list: D053285:CD30 Ligand; D015704:CD4 Antigens; D017730:Ki-1 Antigen; D008024:Ligands; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; C505774:TNFSF8 protein, human; C505775:Tnfsf8 protein, mouse