Lymphotoxin β, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface

The lymphokine tumor necrosis factor (TNF) has a well-defined role as an inducer of inflammatory responses; however, the function of the structurally related molecule lymphotoxin (LTα) is unknown. LTa is present on the surface of activated T, B, and LAK cells as a complex with a 33 kd glycoprotein, and cloning of the cDNA encoding the associated protein, called lymphotoxin β (LTβ), revealed it to be a type II membrane protein with significant homology to TNF, LTα, and the ligand for the CD40 receptor. The gene for LTβ was found next to the TNF-LT locus in the major histocompatibility complex (MHC), a region of the MHC with possible linkage to autoimmune disease. These observations raise the possibility that a surface LTα-LTβ complex may have a specific role in immune regulation distinct from the functions ascribed to TNF.