Pathways of CD4 T cell allorecognition in allograft rejection. (360G-Wellcome-096207_Z_11_Z)

Unique to transplantation, alloantigen originating from engrafted organs can be recognised by recipient CD4 T cells via two distinct pathways: the direct and indirect pathways. It is widely believed that the direct pathway is short lived due to rapid elimination of donor antigen presenting cells soon after transplantation, whereas the indirect pathway is long-lived. Additionally, there is some suggestion that direct pathway CD4 T cells can exert a cytotoxic effector function. These differences h owever, remain largely unproven. This project proposes to definitively characterise the indirect and direct pathways of allorecognition. The key goals include: - To definitively determine the relative duration of direct and indirect allorecognition by CD4 T cells. - To dissect out the role of donor and recipient dendritic cells in priming direct pathway CD4 T cells, and the role of NK cells in regulating the duration and magnitude of this recognition. - To examine the role of B cells in priming direct pathway CD4 T cells. - To provide a model for how late anti-MHC class II alloantibody arises. - To clarify the circumstances in which direct pathway CD4 T cells exhibit effector function and determine role of this in solid organ rejection.