Recombinant Mouse Lymphotoxin alpha2/beta1 Protein, CF

Lymphotoxin-alpha (LT alpha ), also known as tumor necrosis factor (TNF) beta, and lymphotoxin-beta (LT beta ) are members of the TNF family. LT alpha cDNA encodes a 202 amino acid secreted soluble protein with a 33 amino acid signal sequence. LT beta cDNA encodes a 306 amino acid type II membrane protein with an N-terminal cytoplasmic domain (residues 1 - 18), a transmembrane region (residues 29 - 48), and an extracellular domain (residues 49 - 306). Secreted LT alpha assembles as a soluble homotrimer, LT alpha 3. In addition, secreted LT alpha also complexes with the membrane associated LT beta to generate two types of heterotrimers, LT alpha 1/ beta 2 and LT alpha 2/ beta 1 (1). The soluble LT alpha 3 binds both TNF RI (p55) and TNF RII (p75). In contrast, the predominant membrane-bound heterotrimer, LT alpha 1/ beta 2, binds only to the lymphotoxin beta receptor (LT beta R). LT alpha 2/ beta 1 is capable of binding LT beta R, TNF RI (p55), and TNF RII (p75). LT plays a role in normal lymphoid organogenesis (2, 3). Transgenic LT alpha knock-out mice exhibited a loss in lymph node development, a change in splenic architecture, and impaired germinal center formation (4). LT is expressed by activated naïve CD4 cells, unpolarized IL-2-secreting effectors, and Th1 effectors. A loss of LT expression and lack of TNF-alpha or TNF-beta secretion is associated with prior exposure to IL-4 and a Th2 phenotype (5).