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Cholesterol is an important structural and functional component of the plasma membrane. In this review, we focus on T cells and the role of cholesterol in T cell antigen receptor (TCR) signalling, which contributes to autoimmune diseases. Cholesterol binding to the TCR leads to an increased formation of TCR nanoclusters, increasing the avidity of T cells towards the antigen and enabling TCR cooperativity, thus increasing the sensitivity of the T cell. Further, cholesterol is important in the formation of certain lipid nanodomains, called lipid rafts that concentrate signalling molecules and thus also promote TCR signalling. T cell and lipid dysregulation play a key role in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Typically, in SLE, hyper-responsive and exaggerated TCR signalling occurs, partially caused by cholesterol accumulation in the plasma membrane. This might lead to enhanced TCR nanoclustering and lipid raft formation. Thus, targeting lipid metabolism in T cells.