T-Cells Seek Cancer Cells Using the Smallest of Forces; Five Pico- Newtons

In a joint project, the Vienna Science and Technology Fund and the FWF funded an interdisciplinary Viennese team of immunologists, biochemists and biophysicists investigated which mechanical processes are taking place when an antigen is identified.

Specifically, as T cells move, their TCRs are pulling on the antigen with a small force, roughly five pico-newtons.

According to a ScienceDaily report, this is not only adequate to break the bonds between the antigen and the TCRs, but it also helps the T cells as well to find out if they are indeed interacting with the antigen they are looking for.

T-cells play a vital role in one's immune system. Through their TCR or T-cell receptors, as described in the National Library of Medicine, they are making out dangerous cancer cells or invaders in the body and then stimulate an immune response.

On a molecular level, the report specified that this particular recognition process is still not adequately understood.

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Fit For a Particular Antigen

As the study entitled "Temporal analysis of T-cell receptor-imposed forces via quantitative single molecule FRET measurements," published in the Nature Communications journal specified, each of the T cells recognizes a certain antigen specifically well.

According to MedUni Vienna biochemist and immunology professor, Johannes Huppa, to do so, it features approximately 100,000 TCRs of the same sort on its surface.

When viruses are attacking the body, infected cells exhibit different fragments of viral proteins on their surface. More so, T cells are examining such cells for the existence of such antigens.

Such works based on the lock-and-key standard explained Huppa. For each antigen, the professor added, the body needs to produce T cells with corresponding TCRs.

To simply put, each T-cell only recognizes just one particular antigen to then successively stimulate an immune reaction.

'Pull-Away' Behavior

TU Wien Biophysics Professor Gerhard Schutz compared the process with finding out if a particular surface is sticky.

He elaborated, "we then test" the manner of stability the bond has between a finger and that particular surface. One touches then, the latter-mentioned, and pull this finger away until it comes off.

That, Schutz continued, is a good tactic as this pull-away behavior swiftly and simply provides information about the active force present between the surface and the finger.

In principle, T-cells are doing precisely the same. They are not static and they unceasingly deform and their cell membrane is in continuous motion.

Furthermore, when a TCR is binding to an antigen, the cell is exerting a steadily rising pulling force until the binding finally breaks. This can then provide information if it is the antigen that the cell is looking for.

Measurable Process

According to Dr. Janett Gohring, first author of the study at both TU Vienna and MedUni Vienna, this is a measurable process even at the individual molecules' level.

Meanwhile, the two other authors, Dr. Lukas Schrangl and Florian Kellner from TU Vienna and MedUni Vienna respectively explained, a special protein was used for such a process, behaving nearly like a perfect non-spring.

They added that the more traction is employed on the protein, the longer it turns out to be. With special fluorescent marker molecules, one can now gauge how the length of the protein has changed, and that offers information on the forces that take place.

This way, the research team was able to present that T cells are typically exerting a force of a maximum of five pico-newtons, a tiny force that can nonetheless separate the receptor from the antigen.

To compare, one would have to pull on over 100 million such springs at the same time to feel stickiness using a finger.

Related information is shown on Cambridge University's YouTube video below: