LY96

LY96, also known as lymphocyte antigen 96, is a human gene that encodes the secreted glycoprotein MD-2. MD-2 forms a complex with Toll-like receptor 4 (TLR4) on the surface of innate immune cells and is essential for the recognition of lipopolysaccharide (LPS) from Gram-negative bacteria.

Upon exposure to LPS, LPS-binding protein and CD14 deliver LPS to the MD-2/TLR4 complex. Binding of LPS to MD-2 induces dimerization of the TLR4/MD-2 complex and initiates intracellular signaling via MyD88-dependent and TRIF-dependent pathways. This leads to activation of transcription factors such as NF-κB and IRFs and the production of pro-inflammatory cytokines, including TNF, IL-6, and IL-1β, as well as type I interferons.

LY96 expression is strongest in cells of the myeloid lineage, including monocytes, macrophages, and dendritic cells, with detectable but more limited expression in other tissues. The MD-2 protein is a secreted glycoprotein featuring a hydrophobic pocket that binds lipid A, the endotoxic component of LPS, enabling LPS sensing by the TLR4 receptor complex.

Genetic disruption of LY96 or MD-2 impairs LPS responsiveness in animal models and can attenuate LPS-induced sepsis, highlighting its role in innate immunity. Polymorphisms or altered LY96 expression have been investigated for associations with susceptibility to infections and inflammatory diseases, though findings vary across populations.