The impact of genetic risk has been studied for years, however the genetic background is far from deterministic and interaction with environmental factors is needed for MS to evolve. However, which part of the aberrant immune response is guided by either genes or environment is difficult to decipher. With the help of the unique setting of the MS TWIN STUDY we could show that about half of the composition of our immune system is determined by the genetic background. In this project, peripheral blood mononuclear cells of 61 pairs of identical twins with discordance for MS were examined with the use of cutting-edge single-cell technologies and artificial intelligence to describe the immune profiles of the twin pairs in rich detail and with full control of genetic influences. Thereby we could not only identify characteristic proteins in the immune cells of the MS affected twin, but also decode which transcriptional programs are switched on in these cells. Specifically, in the blood of MS twins we detected T cells with characteristics of recently activated cells, which are more likely to migrate into the central nervous system and cause damage there.