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Molecular mechanism that T cell receptors shape the body’s immune response

Molecular mechanism that T cell receptors shape the body’s immune response A research report published in the international magazine eLife, scientists from the University of Basel in Switzerland and other institutions developed a new method through research and development.

To help study the specificity of T cells in the context of infection, in the article, researchers reported different directions taken by the specificity of T cells, depending on whether the patient’s disease occurred in the acute viral infection period (such as influenza) or Occurs during the chronic infection period of the virus (such as HIV infection or malaria), the latter cannot be overcome by the human body.

In the article, the researchers focused on the study of helper T cells. When such cells are activated by viral infection, they can be specialized in one of two ways, that is, become Th1 cells (the T cells that can drive more severe inflammation). Cell killing response) or T follicular helper cells (Tfh cells, which promote antibody production); The balance between Th1 cells and Tfh cells is crucial for studying the degree of the body’s immune response to inflammation.

Molecular mechanism that T cell receptors shape the body's immune response

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Set the tone for the level of activation

However, for helper T cells to decide which path to choose when specializing, the current research of scientists is still relatively weak. One of the factors that may play an important role is the strength of T helper cells being activated, or more precisely their T helper cells. Cell receptors: T cell receptors are molecular sensors located on the surface of cells, which are more or less matched to some pathogens. The better the match, the more receptors are activated.

However, so far, researchers are unlikely to study the role of T cell receptor signal strength in the context of viral infection, because they lack a suitable experimental model; for this reason, the researcher King Others conducted related joint research to solve this problem.

Confrontation of acute and chronic infections

The results of this article surprised researchers very much, that is, the activation of T cell receptors does play a role, but on the contrary, it depends on whether the infection is acute or chronic; in the acute viral infection stage, a stronger activation effect will This leads to the production of more inflammatory Th1 cells. However, in chronic infections, stronger activation will produce more non-inflammatory Tfh cells.

The first author of the article, Dr. Marco Künzli, said that the reason behind this may be an evolutionary adaptation of the body to protect itself. If in chronic infection, too many inflammatory Th1 cells are produced for a long time, it will damage the body’s own organs for a long time.

The longer the stronger

The study in this article also yielded another interesting finding, that is, in chronic infections, Th1 cells formed due to weaker activation are stronger than receptors and cell specializations can maintain their functions for a longer period of time. Perhaps there is a certain correlation, because in the process of chronic infection, Th1 cells will become exhausted over time. Researcher King concluded that the results of this article may help us uncover the mystery of T cell depletion, and in the future will also help researchers develop new therapies for chronic viral infections.

Determining the fate of T cells

In the new method developed by the researchers, they rely on mice carrying T helper cells, which carry the same receptors, which can help identify specific viruses, such as lymphocytic choriomeningitis. Virus (LCMV). The researchers specifically mutated LCMV to express the receptor that strongly activates T cells (at a moderate or weak level). In addition, the researchers also modified two minimally different LCMVs, one of which Can cause acute infection, one can cause chronic infection; then they used different virus mutants to infect mice, and studied the further development of T cells in the blood in the case of acute virus infection and chronic virus infection.