CD30 ANTIGEN, A MARKER FOR HODGKINS LYMPHOMA, IS A RECEPTOR WHOSE LIGAND DEFINES AN EMERGING FAMILY OF CYTOKINES WITH HOMOLOGY TO TNF

CD30 is a surface marker for neoplastic cells of Hodgkin's lymphoma an d shows sequence homology to members of the tumor necrosis factor (TNF ) receptor superfamily. Using a chimeric probe consisting of the extra cellular domain of CD30 fused to truncated immunoglobulin heavy chains , we expression cloned the cDNA cognate from the murine T cell clone 7 B9. The encoded protein is a 239 amino acid type II membrane protein w hose C-terminal domain shows significant homology to TNFalpha, TNFbeta , and the CD40L. Cross-hybridization to an induced peripheral blood T cell cDNA library yielded the human homolog, which is 72% identical at the amino acid level. The recombinant human ligand enhances the proli feration of CD3-activated T cells yet induces differential responses, including cell death, in several CD30+ lymphoma-derived clones. The hu man and murine genes map to 9q33 and the proximal region of chromosome 4, respectively.