Using time-resolved 3D-microscopy methods, Cai et al. found that T cells use highly dynamic microvilli to palpate all spots on the surface of antigen-presenting cells at a rate matching their movement through tissue; upon recognition of a cognate antigen by a TCR, the relevant microvilli were selectively stabilized by TCR microclusters independent of downstream signaling or the cytoskeleton.
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.
Author Info: (1) Department of Pathology, University of California, San Francisco, CA 94143, USA. (2) Department of Pathology, University of California, San Francisco, CA 94143, USA. Biological
Author Info: (1) Department of Pathology, University of California, San Francisco, CA 94143, USA. (2) Department of Pathology, University of California, San Francisco, CA 94143, USA. Biological Imaging Development Center, University of California, San Francisco, CA 94143, USA. (3) Department of Pathology, University of California, San Francisco, CA 94143, USA. (4) Department of Pathology, University of California, San Francisco, CA 94143, USA. (5) Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, CA 94143, USA. (6) Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, CA 94143, USA. (7) Department of Pathology, University of California, San Francisco, CA 94143, USA. (8) Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. (9) Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. (10) Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. (11) Center for Advanced Studies of Blanes (CEAB-CSIC), 17300 Girona, Spain. Ecological and Forestry Applications Research Center (CREAF), 08193 Barcelona, Spain. Institut Catala de Recerca i Estudis Avancats (ICREA), 08010 Barcelona, Spain. (12) Department of Pathology, University of California, San Francisco, CA 94143, USA. matthew.krummel@ucsf.edu. Biological Imaging Development Center, University of California, San Francisco, CA 94143, USA.
