puc-header

Durable Interactions of T Cells With T Cell Receptor Stimuli in the Absence of a Stable Immunological Synapse

36 Pages Posted: 7 Apr 2018 Sneak Peek Status: Published

See all articles by Viveka Mayya

Viveka Mayya

University of Oxford - Kennedy Institute of Rheumatology; New York University (NYU) - Skirball Institute of Biomolecular Medicine

Edward Judokusumo

Columbia University - Department of Biological Engineering

Willie Neiswanger

Carnegie Mellon University - Machine Learning Department; Columbia University - Department of Applied Physics and Applied Mathematics

David Depoil

University of Oxford - Kennedy Institute of Rheumatology

David A. Blair

New York University (NYU) - Skirball Institute of Biomolecular Medicine

Chris H. Wiggins

Columbia University - Department of Applied Physics and Applied Mathematics

Lance C. Kam

Columbia University - Department of Biological Engineering

Michael L. Dustin

University of Oxford - Kennedy Institute of Rheumatology; New York University (NYU) - Skirball Institute of Biomolecular Medicine

More...

Abstract

T cells engage in two modes of adhesive interaction with antigen presenting cells (APC) and surfaces: stable synapses and motile kinapses. While it is surmised that durable interactions observed between T cells and spatially isolated APCs involve stable synapses, in situ 3D imaging cannot resolve the mode of interaction. We have established in vitro platforms and quantitative metrics to determine cell-intrinsic modes of interaction when T cells are faced with spatially continuous or restricted stimulation. Human naïve CD8 and CD4, memory CD4, and murine naïve and memory CD8 T cells formed kinapses, whereas only the human memory CD8 T cells formed synapses on spatially uniform stimulatory 2D surfaces. Surprisingly, we did not observe any concordant relationship between the mode and durability of interaction exhibited by the human T cell subsets on cell-sized stimulatory spots. The human naïve CD8 T cells maintain kinapses for more than three hours while persisting on the stimulatory spots for longer than their memory counterparts that maintain synapses. Thus, our results demonstrate that durable interactions do not require stable synapses.

Suggested Citation

Mayya, Viveka and Judokusumo, Edward and Neiswanger, Willie and Depoil, David and Blair, David A. and Wiggins, Chris H. and Kam, Lance C. and Dustin, Michael L., Durable Interactions of T Cells With T Cell Receptor Stimuli in the Absence of a Stable Immunological Synapse (2018). Available at SSRN: https://ssrn.com/abstract=3155633 or http://dx.doi.org/10.2139/ssrn.3155633
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Viveka Mayya

University of Oxford - Kennedy Institute of Rheumatology

Roosevelt Drive
Headington
Oxford, England OX3 7FY
United Kingdom

New York University (NYU) - Skirball Institute of Biomolecular Medicine

540 First Avenue
New York, NY 10016
United States

Edward Judokusumo

Columbia University - Department of Biological Engineering

500 W. 120th St.
351 Engineering Terrace
New York, NY 10027
United States

Willie Neiswanger

Carnegie Mellon University - Machine Learning Department

Gates Hillman Center
5000 Forbes Ave 8th
Pittsburgh, PA 15213-3891
United States

Columbia University - Department of Applied Physics and Applied Mathematics

New York, NY 10027
United States

David Depoil

University of Oxford - Kennedy Institute of Rheumatology

Roosevelt Drive
Headington
Oxford, England OX3 7FY
United Kingdom

David A. Blair

New York University (NYU) - Skirball Institute of Biomolecular Medicine

540 First Avenue
New York, NY 10016
United States

Chris H. Wiggins

Columbia University - Department of Applied Physics and Applied Mathematics

New York, NY 10027
United States

Lance C. Kam

Columbia University - Department of Biological Engineering

500 W. 120th St.
351 Engineering Terrace
New York, NY 10027
United States

Michael L. Dustin (Contact Author)

University of Oxford - Kennedy Institute of Rheumatology ( email )

Roosevelt Drive
Headington
Oxford, England OX3 7FY
United Kingdom

New York University (NYU) - Skirball Institute of Biomolecular Medicine

540 First Avenue
New York, NY 10016
United States

Click here to go to Cell.com

Go to Cell.com

Paper statistics

Abstract Views
88
Downloads
5