Durable Interactions of T Cells with T Cell Receptor Stimuli in the Absence of a Stable Immunological Synapse
Viveka Mayya,
Edward Judokusumo,
Enas Abu Shah,
Christopher G. Peel,
Willie Neiswanger,
David Depoil,
David A. Blair,
Chris H. Wiggins,
Lance C. Kam,
Michael L. Dustin
Affiliations
Viveka Mayya
Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK; Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Edward Judokusumo
Department of Biological Engineering, Columbia University, New York, NY 10027, USA
Enas Abu Shah
Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK
Christopher G. Peel
Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK
Willie Neiswanger
Machine Learning Department, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY 10027, USA
David Depoil
Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK
David A. Blair
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Chris H. Wiggins
Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY 10027, USA
Lance C. Kam
Department of Biological Engineering, Columbia University, New York, NY 10027, USA
Michael L. Dustin
Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK; Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA; Corresponding author
Summary: T cells engage in two modes of interaction with antigen-presenting surfaces: stable synapses and motile kinapses. Although it is surmised that durable interactions of T cells with antigen-presenting cells involve synapses, in situ 3D imaging cannot resolve the mode of interaction. We have established in vitro 2D platforms and quantitative metrics to determine cell-intrinsic modes of interaction when T cells are faced with spatially continuous or restricted stimulation. All major resting human T cell subsets, except memory CD8 T cells, spend more time in the kinapse mode on continuous stimulatory surfaces. Surprisingly, we did not observe any concordant relationship between the mode and durability of interaction on cell-sized stimulatory spots. Naive CD8 T cells maintain kinapses for more than 3 hr before leaving stimulatory spots, whereas their memory counterparts maintain synapses for only an hour before leaving. Thus, durable interactions do not require stable synapses. : T cells primarily form two types of adhesive junctions when interacting with stimulatory surfaces: stable synapses and motile kinapses. Mayya et al. demonstrate that durable interactions with antigen do not require formation of a stable synapse. Keywords: lymphocytes, migration, immunological synapse, kinapse, chemokines, adhesion, live imaging, micro-contact printing
