**4.3 Direct pathway**

In the direct pathway, host T cells recognize intact allo-MHC molecules on the surface of the donor cells or APCs. Mechanistically, host T cells see allo-MHC molecule + allo-peptide as being equivalent in shape to self-MHC + foreign peptide; therefore, host T cells recognize the donor tissue as foreign. This pathway is presumably the dominant pathway involved in early alloimmune responses.

The transplanted organ carries a variable number of passenger APCs in the form of interstitial dendritic cells. Such APCs have a high density of allo-MHC molecules and are capable of directly stimulating recipient T cells. The relative number of T cells that proliferate on contact with allogeneic or donor cells is extraordinarily high compared to the number of clones that target antigens presented by self-APCs. Thus, this pathway is important in acute allorejection.
