LAT Human

The LAT gene is located on chromosome 16 in humans . The protein encoded by this gene is a transmembrane protein that localizes to lipid rafts, also known as glycosphingolipid-enriched microdomains (GEMs). These lipid rafts are specialized membrane microdomains that play a key role in cellular signaling.

LAT plays a pivotal role in the diversification of T cell signaling pathways following the activation of the TCR signal transduction pathway. When the TCR binds to the major histocompatibility complex (MHC) class II, it triggers the initial activation of T cells . Upon phosphorylation, LAT recruits multiple adaptor proteins and downstream signaling molecules into multimolecular signaling complexes located near the site of TCR engagement .

In T cells, LAT is rapidly tyrosine-phosphorylated in response to the crosslinking of the TCR. This phosphorylation event allows LAT to associate with various Src homology 2 (SH2) domain-containing proteins, including phospholipase C (PLC)-γ1, Vav, SLP76, Grb2, and the 85 kDa regulatory subunit of PI3 kinase . These interactions are essential for linking proximal tyrosine phosphorylation to downstream signaling events.

The activation of T cells is a complex process that involves multiple signaling pathways. LAT serves as a critical adaptor protein that links the TCR to downstream signaling pathways, facilitating the activation and differentiation of T cells . In the absence of functional LAT or its phosphorylation, T cell development is severely impaired, highlighting its essential role in the immune response .

Recombinant human LAT has been studied for its potential therapeutic applications, particularly in the context of adoptive cell therapy (ACT) and chimeric antigen receptor (CAR)-T cell therapy. These therapies involve the genetic modification of T cells to enhance their ability to target and destroy cancer cells . By incorporating LAT into these therapies, researchers aim to improve T cell persistence, engraftment, and overall clinical outcomes .