Why can a small point mutation have a very large effect on the characteristics of T cells?

  T cells play an important role in the function of the human immune system. T cells can accurately and effectively distinguish diseases and foreign bodies from the body's own healthy tissues, and at the same time trigger actions required to respond to certain outpatient invasion activities. The details of this immune response vary, but researchers currently do not understand each step. Scientists at Würzburg University and other institutions have revealed new details in these processes through their research. The researchers found that mutations in small spots in the gene can modify T cells and no longer have such strong protective properties. Of course, this may be an advantage that can help control the serious side effects of the patient's body after stem cell transplantation (including T cell infusion). When T cells detect foreign bodies or altered tissue, they trigger an immune response, such as infection or tumor tissue. This is usually done through receptors on the cell surface. These T cell receptors then send signals to the cells to initiate an immune response. The first step is to activate a special transcription factor family, which activates the nuclear factor NFAT in T cells. Then, NFAT collects the DNA in the nucleus and induces the production of cytokines (such as interleukin 2).

  FAT is made up of different families, and may have some overlapping tasks or perform completely different functions, but this does not seem to be all. Like many other proteins in cells, they can be modified after synthesis. In order to customize its function, in a recently published study, researchers studied the special changes in NFATc1 family members, namely SUMOylation changes. Researcher Friederike Berberich-Siebelt explained that ubiquitin-like modifications play an important role in a variety of cellular processes such as nuclear transport, programmed cell death and antiviral mechanisms. In addition, researchers are studying cancer and herpes virus infection. In many diseases, the modification process similar to ubiquitin is lacking.

  In this study, the researchers conducted related research on experimental animals. These animals have two non-essential point mutations in the NFATc1 gene, but these mutations hinder the development of modifications, such as ubiquitination. Not necessarily a disadvantage. Researchers have found that the offspring of these animals are very healthy, and the modified NFATc1 can even mediate specific signal transduction pathways, thereby causing at least the clinical manifestations of multiple sclerosis in animal models. He said it could be reduced. When T cells with these mutations are used in the process of stem cell transplantation, they attack host animal tissues much less than normal cells. This effect is due to the increase in interleukin-2 levels at the beginning of the immune response at the biomolecular level. Interleukin-2 can counteract the process of T differentiation into inflammatory T cell subtypes and support the so-called regulation. The production of T cells, this research was found to be of great significance to later scientists for stem cell transplantation (including T cell infusion). The researchers pointed out that it can effectively prevent the use of T cells that have not been modified by NFATc1 ubiquitination. The occurrence of side effects indicates that point mutations may have a greater impact. In order to do more detailed research, the researchers continue to study the feasibility and feasibility of the treatment at a later stage, while using CRISPR/Cas9 gene editing technology to edit human T cells. The process of hematopoietic stem cell transplantation also wants to know whether it can be manufactured and it shows the correct activity. The results of this study may not be related to the potential outcome of the treatment application. Finally, the researchers said that they are very interested in understanding the mechanisms of cell microregulation, such as T cell receptor signaling and the function of NFAT family members and their subtypes. In fact, the mutations and subtle direct effects of two harmless points may be enough to transform from inflammation, autoimmunity, and rejection to body tolerance. At the beginning of the immune response, it is sufficient to complete a small focus shift.