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Biological Chemistry

T cells tug on antigens

Tiny forces could help immune cells discriminate between friend and foe

by Michael Torrice
May 16, 2016 | APPEARED IN VOLUME 94, ISSUE 20

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Credit: Science
A DNA hairpin-based force sensor is attached to a gold nanoparticle on one end and an MHC on the other. When a T cell tugs on the MHC, the DNA hairpin unfolds and a fluorophore (red dot) is pulled away from a quencher (black dot) and the gold nanoparticle, causing the fluorophore to glow.
Credit: Science
A DNA hairpin-based force sensor is attached to a gold nanoparticle on one end and an MHC on the other. When a T cell tugs on the MHC, the DNA hairpin unfolds and a fluorophore (red dot) is pulled away from a quencher (black dot) and the gold nanoparticle, causing the fluorophore to glow.

T cells patrol the body looking for invading pathogens by crawling along cells and binding to antigens displayed on the cells’ surfaces. A new study suggests that T-cell receptors may tug on those antigens to help discriminate between antigens from the body and those from invaders (Proc. Natl. Acad. Sci. USA 2016, DOI: 10.1073/pnas.1600163113). Researchers previously have shown that mechanical forces alter interactions between T-cell receptors and antigens presented by surface proteins called major histocompatibility complex (MHC). Khalid Salaita of Emory University and colleagues wanted to see if T cells transmit such forces to their receptors and for what purpose. They created force sensors based on DNA hairpins immobilized on gold nanoparticles. With a certain amount of force, the hairpin unfolds, allowing a fluorescent dye to glow by pulling it away from molecules that quench it. By using these sensors and fluorescence microscopy, the team determined that T-cell receptors exert between 12 and 19 pN of force on individual antigen-presenting MHCs. They also showed that dampening this force eliminated T cells’ ability to discriminate between antigens that would trigger strong and weak immune responses.

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