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It is impossible to survive without T cells. In our immune system, T cells are a key component. The surface of these cells contains highly sensitive receptors; pathogens can be detected from the surface of these cells. We could not completely understand the exact mechanism through which these receptors could be distributed on the surface of T cells; however, TU Wien performed analyses to prove that tenacity of previous ideas could not be ensured.

According to previous studies, certain points of receptors would be concentrated with T cells. The main objective would be to detect receptors with the highest possible sensitivity. In a current publication, TU Wien published the findings of a biophysics research group. In this experiment, the reaction could be carried out quickly by actually programming T cells; therefore, the receptors could be arranged in a random manner.

These results indicate that there exists a close collaboration between following institutions: the Medical University of Vienna (MUW) and the Max Planck Institute (MPI) of Biophysics in Göttingen, Germany. With these new findings, we could better understand immune responses of T cells; moreover, new methods of medical treatment can also be developed. In the specialist journal Nature Immunology, we have published these findings.

A needle in a haystack

A T cell is a molecular detector of high specificity. Prof. Gerhard Schütz is the head of biophysics research group, which is affiliated to the Institute of Applied Physics at TU Wien. Each T cell can be reacted with a very specific molecule; however, many different T cells are required for the functioning of our bodies. Several thousand copies of the same receptor are present on the surface of each T cell.

The T cell would still need an important partner to trigger an immune reaction; this partner is termed as the antigen-presenting cell. The surfaces of these cells contain many different molecules, which assist several carrier proteins. Several molecules originated from endogenous structures, and these structures were harmless in nature; however, characteristic antigens of harmful intruders were also transported by the body on these cells that contained antigens.

When one of these antigen-presenting cells comes into contact with T cell, we begin the search for a needle in a haystack. The T cell was programmed for a molecule of the exact type. This T cell was found among several hundreds of thousands of molecules, which were present on the surface of an antigen-presenting cell. Suppose countless versions of the same key were present on the surface of a T cell. Now, we have to quickly determine whether the same key would fit into any of the hundreds of thousands of locks, which were present on the antigen-presenting cell.

Speed counts

We have discussed how T cells could manage to react with such extreme sensitivity to very specific antigens, which are present in an extremely small amount. One of the most widely proposed theory is summarized as follows: several receptors on the T-cell surface were locally concentrated in the form of clusters.

These receptors would then manage to dock a specific antigen with more precision. Several modern high-performance microscopic methods could be improved to such an extent that we could manage to take images of T-cell surfaces for the first time. This theory was confirmed completely. Irregular structures were observed on T-cell surfaces, which were considered as receptor clusters.

This conclusion was slightly premature in terms of its outreach. After closely examining T cells, all of our efforts were focused on improving microscopic methods. Previous studies had observed clusters of several receptors, which were probably slightly greater than an artefact; however, the same receptor molecule could be easily conceptualized several times.”

After conducting the analyses at TU Wien, another theory was suggested: The receptors were distributed randomly over T cell. The immune reaction occurs so quickly. The antigen-presenting cells could easily come into contact with T cell; however, the T cell would always have a ‘key’ to fit into the ‘lock’ at this location. If this is correct, the two cells would not lose any time by getting into the right position; however, the immune reaction would be triggered immediately.

We are continuously working toward establishing the outer limits of possibility. For this purpose, we used modern methods of microscopy. This finding is path-breaking in the field of immunology. To have a better understanding of T-cell surface, we first need to identify the pathogens that provide a better understanding of the surface. Our findings could be then coupled with other findings in immunotherapy.