Cutting Edge: Allograft Rejection is Associated with Weak T Cell Responses to Many Different Graft Leukocyte-Derived Peptides

Organ transplants are rapidly rejected because T cells in the recipient attack the foreign MHC molecules on the graft. The robustness of the T cell response to histoincom-patible tissue is not understood. We found that mice have many small T cell populations with Ag receptors specific for a foreign MHC class II molecule type loaded with pep-tides from leukocytes from the graft. These T cells proliferated modestly after skin transplantation and underwent relatively weak functional differentiation compared with T cells stimulated by a vaccine. Thus, the potency of the T cell response to histoincompatible tissue is likely due to many small T cell populations responding weakly to hundreds of MHC-bound peptides from graft-derived leukocytes.