2021
DOI: 10.1101/2021.08.18.456686
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Visualizing and manipulating hyperstabilization of T cell microvilli contacts by engineered chimeric antigen receptors

Abstract: T cells typically recognize their ligands using microvilli to scan for cognate antigen and scaffold T cell receptors (TCRs) during antigen recognition. Conventional chimeric antigen receptors (CARs) are often built using single-chain variable fragments (scFvs) with far greater affinity than that of natural TCRs. The implications of this for T cell function are not well understood. Using high-resolution microscopy, we studied the membrane dynamics in cells bearing anti-human epidermal growth factor receptor 2 (… Show more

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Cited by 1 publication
(4 citation statements)
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“…Visualization of microvilli on Jurkat T cells expressing a fluorescent protein-conjugated TCRz by Airyscan confocal microscopy revealed high concentrations of TCRs, which specifically accumulated at the microvilli tips (Figure 1D) (46). Using LLSM, accumulation of endogenous TCRs and chimeric antigen receptors (CARs) on CAR-transduced human CD8 + T cell blasts were also observed in 50% and 87% of microvilli tips, respectively (54). However, in ovalbumin-specific TCR transgenic OT-I mice, TCR nano-clusters on CD8 + T cells were not restricted to microvilli, but increased microvilli occupancy was observed upon activation (55).…”
Section: Pre-existing Clusters Of T Cell Receptorsmentioning
confidence: 99%
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“…Visualization of microvilli on Jurkat T cells expressing a fluorescent protein-conjugated TCRz by Airyscan confocal microscopy revealed high concentrations of TCRs, which specifically accumulated at the microvilli tips (Figure 1D) (46). Using LLSM, accumulation of endogenous TCRs and chimeric antigen receptors (CARs) on CAR-transduced human CD8 + T cell blasts were also observed in 50% and 87% of microvilli tips, respectively (54). However, in ovalbumin-specific TCR transgenic OT-I mice, TCR nano-clusters on CD8 + T cells were not restricted to microvilli, but increased microvilli occupancy was observed upon activation (55).…”
Section: Pre-existing Clusters Of T Cell Receptorsmentioning
confidence: 99%
“…Our understanding of the underlying mechanisms and functional consequences of microvilli in T cell immunity has recently expanded (125,(146)(147)(148)(149). It has been demonstrated that microvilli-mediated contacts induce initial calcium triggering (25,(150)(151)(152) and that stabilization of the microvillimediated close contacts affects effector functions (54,152). A study using nonporous membranes with varying pore depths, sizes, and interpore distances showed that microvilli confined in 200-nm pores altered gene expression and segregation of signaling molecules that lead to T cell activation and proliferation (153).…”
Section: Implications and Conclusionmentioning
confidence: 99%
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