Jean Paul Soullilou | Institute de Transplantation | Nantes, France

Nantes, France

Autoimmune diseases are characterized by autoreactive T cells which can be identified by their function or phenotypes. Complex alterations of chain T cell receptor (TCR) repertoires for antigens (including auto-antigens) can be detected during auto immune response and tolerance states. The following in time of these changes can theoretically provide important information for diagnostic, disease activity and the effect of treatment, including regimens aimed at inducing immune tolerance against auto antigens (deletion of autoreactive clones for instance). However, because of the flexibility and adaptability of TCR recognition (cross recognition), auto immune T cells are not clonally distributed and strongly selected T cell cohorts without apparent clonality are also important to consider. To date, analysis of auto-antigen induced biases in TCR V(beta) segment usage can be routinely identified by Immunoscope/ Spectratype methods. However, these methods do not provide information on the amount of mRNA concerned (reflecting the size and the activation of the autoreactive T cell pools). In addition they only provide independent information for each of the V(beta) family. New tools such as tetramers will be very useful but require a precise knowledge of a dominant peptide and a specific restricting MHC.We propose a new approach that integrates qualitative and quantitative variations of T cell receptor antigens in T lymphocytes. In addition, we express these integrated alterations as a global landscape (Tc Land© including all V(beta) transcriptome). This approach, that we have validated in man in vitro and in vitro/in vivo in the rat (rejection/tolerance of allograft) has never been used before. Using this method, we want to study landscape of blood T lymphocytes in a cohort of 30 patients with active forms of MS, an auto immune disease in which T cells reacting against myelin determinants are believed to be instrumental. We hope to demonstrate, at the level of each patient (since the T cell receptor usage is individually shaped), patterns specific for their disease and to relate them to the disease activity. If we can obtain such " TCR signature ", we will, in a second time, use it to follow regulation of auto reactive T cells, particularly during tolerance induction. The approach can be theoretically extended to other auto immune diseases and to transplantation.