Visualizing dynamic microvillar search and stabilization during ligand detection by T cells.

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• T cells perform immune surveillance by interacting with antigen-presenting cells.
• T cells must balance search speed and sensitivity when identifying peptide-loaded major histocompatibility complexes (pMHCs).
• The precise role of T cell microvilli in this search process has remained largely unknown.

Purpose of the Study:

• To elucidate the microvillar strategy employed by T cells during immune surveillance.
• To understand how T cells achieve efficient searching and sensitive detection of pMHCs.

Main Methods:

• Utilized lattice light-sheet microscopy for high-resolution imaging.
• Employed quantum dot-enabled synaptic contact mapping to track molecular interactions.
• Analyzed microvillar dynamics, diffusion patterns, and fractal organization.

Main Results:

• Demonstrated anomalous diffusion and fractal organization of microvilli enable rapid surveying of surfaces within one minute.
• Showed that T cell receptor (TCR) accumulation stabilizes microvilli, with dwell times sufficient for discriminating pMHC half-lives.
• Found microvillar stabilization is independent of tyrosine kinase signaling and the actin cytoskeleton, indicating selection for TCR microclusters.

Conclusions:

• T cell microvilli are crucial sensory organs that facilitate efficient and sensitive immune surveillance.
• Microvillar stabilization by TCRs represents a key mechanism for ligand detection, independent of traditional signaling pathways.
• This study defines an efficient cellular search strategy fundamental to T cell function and immune response.