HLA system in solid organ transplantation part 11

Following transplantation, the alloreactive T cells from the recipient  can be activated directly by the donor APC, bearing intact surface allogeneic MHC molecules, that migrated from the graft into the lymphoid tissue of the recipient (direct pathway of allorecognition).Alternatively, alloreactive T cells can be stimulated indirectly by recipient APC taking up alloantigens  derived from the donor tissue, which can be MHC molecules or other polymorphic molecules, digesting them into peptides and conjugating them to their own MHC molecules and present them to other alloreactive T cells (indirect pathway of allorecognition). The direct pathway of allorecognition  is the initial pathway of T cells allostimulation and it is very powerful. It was initially though that this pathway started to fade away once the short-lived donor-derived APC started to perish in the recipient, and then the indirect pathway of allorecognition was the dominant pathway driving T cell activation throughout the life of the transplant. However, it has been demonstrated that recipient APC are able to uptake entire  allogeneic MHC molecules from donot-derived cells in the transplant and present them successfully to alloreactive T cells generated through the direct pathway of allorecognition, allowing the persistence of directly-activated T cells throughout the life of the transplant. This pathway has been referred to as semi-direct pathway of allorecognition.