CD6 is a type I transmembrane glycoprotein with a molecular mass of 105–130 kDa. It is composed of an extracellular region with three tandem scavenger receptor cysteine-rich (SRCR) domains, a transmembrane region, and a cytoplasmic tail with several phosphorylatable residues suitable for intracellular signal transduction. CD6 associates with the TCR/CD3 complex and plays a role in stabilizing adhesive contacts with antigen-presenting cells (APCs), modulating subsequent TCR/CD3 intracellular signals that drive proliferative and differentiation responses. CD6 also interacts with several ligands, including CD166/ALCAM, CD318/CDCP1, and galectins 1 and 3. These interactions are important for various T cell physiological processes such as thymocyte development, T-APC immunological synapse stabilization, and T cell transmigration to inflamed tissues. Moreover, CD6 has been implicated in various autoimmune diseases. It was identified as a susceptibility locus in multiple sclerosis and Behcet's disease. The role of CD6 in autoimmune diseases may specifically reflect its interaction with CD318, which is expressed on key tissue cells in these diseases.
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