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

• Published in: Science (American Association for the Advancement of Science) Vol. 356; no. 6338; p. 598
• Main Authors: Cai, En, Marchuk, Kyle, Beemiller, Peter, Beppler, Casey, Rubashkin, Matthew G., Weaver, Valerie M., Gérard, Audrey, Liu, Tsung-Li, Chen, Bi-Chang, Betzig, Eric, Bartumeus, Frederic, Krummel, F.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 12.05.2017; The American Association for the Advancement of Science; American Association for the Advancement of Science (AAAS)
• Subjects: Actin; Actin Cytoskeleton - metabolism; Adaptive immunity; Animals; Antigen-presenting cells; Antigens; Antigens - immunology; Apposition; Binding; Cell recognition; Cell surface; Cell-mediated immunity; Complex formation; Contact; Cytoskeleton; Deformation effects; Dimensional analysis; Dwell time; Fractals; Half-life; Histocompatibility; Immune response; Immune response (cell-mediated); Immunological synapses; Immunology; Immunosurveillance; Information Seeking; Kinases; Latency; Life Sciences; Ligands; Light sheets; Lymph nodes; Lymphocytes; Lymphocytes T; Mapping; Mathematical analysis; Mice; Microscopy; Microscopy - methods; Microvilli - chemistry; Microvilli - metabolism; Microvillus; Organs; Physiology; Protein-tyrosine kinase; Quantum Dots; Real time; Receptors; Receptors, Antigen, T-Cell - metabolism; Recognition; RESEARCH ARTICLE SUMMARY; Scanning; Search Strategies; Searching; Sense organs; Sensitivity; Stabilization; T cell receptors; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tissues; Topology; Tradeoffs; Tyrosine
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aal3118

During immune surveillance, T cells survey the surface of antigen-presenting cells. In searching for peptide-loaded major histocompatibility complexes (pMHCs), they must solve a classic trade-off between speed and sensitivity. It has long been supposed that microvilli on T cells act as sensory organs to enable search, but their strategy has been unknown. We used lattice light-sheet and quantum dot-enabled synaptic contact mapping microscopy to show that anomalous diffusion and fractal organization of microvilli survey the majority of opposing surfaces within 1 minute. Individual dwell times were long enough to discriminate pMHC half-lives and T cell receptor (TCR) accumulation selectively stabilized microvilli. Stabilization was independent of tyrosine kinase signaling and the actin cytoskeleton, suggesting selection for avid TCR microclusters. This work defines the efficient cellular search process against which ligand detection takes place.