Abstract
Two related models for T cell signalling initiation suggest either that T cell receptor (TCR) engagement leads to its recruitment to ordered membrane domains, often referred to as lipid rafts, where signalling molecules are enriched or that ordered TCR-containing membrane nanodomains coalesce upon TCR engagement. That ordered domains form upon TCR engagement, as they do upon lipid raft marker patching, has not been considered. The target of this study was to differentiate between those three options. Plasma membrane order was followed in live T cells at 37 °C using laurdan to report on lipid packing. Patching of the TCR that elicits a signalling response resulted in aggregation, not formation, of ordered plasma membrane domains in both Jurkat and primary T cells. The TCR colocalised with actin filaments at the plasma membrane in unstimulated Jurkat T cells, consistent with it being localised to ordered membrane domains. The colocalisation was most prominent in cells in G1 phase when the cells are ready to commit to proliferation. At other cell cycle phases the TCR was mainly found at perinuclear membranes. Our study suggests that the TCR resides in ordered plasma membrane domains that are linked to actin filaments and aggregate upon TCR engagement.
Highlights
Two related models for T cell signalling initiation suggest either that T cell receptor (TCR) engagement leads to its recruitment to ordered membrane domains, often referred to as lipid rafts, where signalling molecules are enriched or that ordered TCR-containing membrane nanodomains coalesce upon TCR engagement
The first is that the TCR is recruited to ordered plasma membrane nanodomains upon its engagement, the second that the TCR always resides in ordered plasma membrane domains and the third that ordered plasma membrane domains form upon engagement of the TCR
Similar results were obtained upon TCR-patching of human primary T cells (Fig. 2), strengthening the conclusion that the TCR is found in ordered membrane domains in resting T cells
Summary
Two related models for T cell signalling initiation suggest either that T cell receptor (TCR) engagement leads to its recruitment to ordered membrane domains, often referred to as lipid rafts, where signalling molecules are enriched or that ordered TCR-containing membrane nanodomains coalesce upon TCR engagement. Often referred to as lipid rafts, are implicated in immune cell signalling They are considered to form by the self-aggregation of cholesterol and sphingolipids[1] and are believed to exist as liquid ordered (lo) domains, in contrast to the rest of the membrane that exists liquid disordered (ld) domains. Downstream signalling involves the activation of Ras and calcium pathways All these pathways can be activated by crosslinking different lipid raft components, the ganglioside GM1 or the GPI-anchored protein CD59, suggesting a link between the aggregation of ordered membrane nanodomains and early T cell signalling[2,3,4]. The lipid packing in the TCR-containing microclusters has not been studied
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