Research Group

  • Prof. Jean-Paul Soulillou, Principal Investigator
  • Dr. Abdel Saoudhi, Research Associate
  • Dr. Marina Guillet, Research Associate
  • Dr. David Laplaud, Research Associate
  • Dr. Annaick Palier, Research Associate
  • Dr. Marc André Delsuc, Research Associate
  • Dr. Claire Usual, Research Associate
  • Dr. Gilles Benichou, Consultant
  • Dr. Samia Khoury, Consultant

Location

  • ITERT, Nantes, France

Title

  • Integrated TCR Vβ Transcriptome Analysis, a New Method to Follow Allo- or Auto-Immune Responses

Organ transplantation allows patients with end stage diseases of a vital organ to recover a normal life. Immune recognition of foreign tissues remains the main obstacle to transplantations that require long-term immunosuppression. The initial alloimmune responses proceed through the usual pathway of immunity in which allopeptides are presented by self-MHC. However, an unusually high proportion of naive T cells also directly recognises foreign MHC. This "direct" recognition is supposed to play a major role in acute rejection early after grafting. Normal recognition (self-APC) is supposed to operate in chronic rejection.

Our programme deals with a global representation of TCR usages in direct and indirect pathways in vitro and in vivo. So far, TCR biases were only studied through qualitative TCR alteration of the Vβ chain segment (CDR3) that interact with peptide/MHC. This is relevant for analysing TCR biases in the indirect pathway, but not in the direct pathway where CDR3 may not be involved. In addition, in all cases the possible relevance of qualitative alteration must benefit from the knowledge of the number of clones involved (i.e. reflected by the amount of mRNA). We propose another approach that links qualitative and quantitative parameters and allows a global assessment of TCR alterations in which qualitative alterations of Vβ mRNA are corrected by the amount of altered mRNA assessed by quantitative PCR.

Our first aim is to optimise this new method. The method will then be used to revisit allo recognition in vitro in direct-type MLR where pure T cells are confronted with allogeneic APC, and in vivo during acute rejection of heart allografts in rat and in an established model of experimental tolerance induction.