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Mohamed Sayegh's research work has focused on the mechanisms of the immune response to alloantigen (allorecognition), and the mechanisms of tolerance induction in experimental models of transplantation and in humans. Specifically, he is studying the role of T cell recognition of processed alloantigen (donor-derived peptides) in allograft rejection, and investigating novel approaches for induction of transplantation tolerance based on T cell costimulatory blockade. Other areas of interest include the role of cytokines in allograft rejection and tolerance, the immunopathogenesis of chronic rejection and the mechanisms of islet allograft destruction in autoimmune diabetes.
The Sayegh laboratory's research interests include the direct and indirect pathways of allorecognition in rejection and tolerance. In the direct pathway, T-cells recognize intact allo-MCH molecules on the surface of donor cells. Proteins, including MCH molecules, bound into the groove of the MCH appear to play an important role in this process. In the indirect pathway, T-cells recognize processed alloantigens presented as peptides by the recipient's antigen-presenting cells (APCs). The lab has demonstrated that the indirect pathway occurs during allograft and xenograft rejection. Thus, it plays an important role in the rejection process, particularly in chronic rejection.
Sayegh's team is also investigating the role of T-cell costimulation in transplantation and autoimmune diseases. They are focuising on the role of CD28-B7 and CD40-CD40L families of costimulatory molecules, not only in allograft rejection but also in diabetes and other autoimmune diseases. They are also exploring ways of blocking these pathways to prevent acute rejection, treat chronic rejection, and treat autoimmune diseases.
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