CHARACTERIZATION OF A NOVEL TNF-LIKE LIGAND AND RECENTLY DESCRIBED TNF LIGAND AND TNF RECEPTOR SUPERFAMILY GENES AND THEIR CONSTITUTIVE ANDINDUCIBLE EXPRESSION IN HEMATOPOIETIC AND NONHEMATOPOIETIC CELLS

A novel (TL1), a recently described (TL2) TNF-like, and three recently described TNF receptor-like (TR1, TR2, TR3) molecules were identified by searching a cDNA database. TL1 and TL2 are type-II membrane protei ns. TR2 and TR3 are type-I membrane proteins whereas TR1 appears to be a secreted protein. TL1, TL2, TR2 and TR3 were expressed in hematopoi etic cells, whereas TR1 was not. Northern blots hybridized with the cD NA probes revealed multiple forms of RNA as well as inducible expressi on of TL1, TL2, TR2 and TR3. TL2 and TR3, in particular, were highly i nduced in activated CD4(+) T cells. Radiation hybrid mapping localized TR1 and TL2 to 8q24 and 3q26, respectively, which are not near any kn own superfamily members. TL1 was mapped to 9q32, near CD30L (9q33) and TR2 and TR3 mapped to the region of chromosome 1 that contains the TN FR-II, 4-1BB, OX40 and CD30 gene cluster at 1p36. Only TR3 in this clu ster possesses a death domain. Southern blot analysis revealed the pre sence of TL and TR genes in different mammalian species. TL2, TR1, TR2 and TR3 were recently described by others as TRAIL/Apo-2L, OPG, HVEM and DR3/WSL-1/Apo-3/TRAMP/LARD, respectively. (C) 1997 Elsevier Scienc e B.V.