T cell memory and Tolerance
T cells are a central compartment of adaptive immunity, which is characterised by the establishment of a memory for previously encountered antigens. T cells develop responses when they recognise cognate non-self antigens, become activated and differentiate into effector cells. Once the antigens have been cleared, the reactive T cells generate memory cells. On the other hand, under certain circumstances, T cells tolerate antigens by not responding to them through various mechanisms, for instances central tolerance (in the case of self-antigens), ignorance and anergy (in the case of peripheral self-antigens). Despite this well-established knowledge of memory and tolerance, the exact mechanisms underlying T cell memory and tolerance are not fully understood.
Under transplantation conditions, the generation of tolerance to donor-derived antigens is essential for successful transplantation while preserving immunity to pathogen-associated antigens. In transplantation between MHC-mismatched unrelated donors and recipients, T-cell responses to minor histocompatibility antigens (minor H Ags) are a major obstacle to MHC-mismatched solid tissue and bone marrow transplantation. From an antigenic standpoint, transplantation between MHC-matched individuals has the potential to be remarkably complex. However, the magnitude of the immune response is simplified by the phenomenon of immunodominance. Among the many dominant minor H Ags identified, H60 stands out as an extremely dominant antigen, overwhelming T cell responses to H28, H4, H13, H7 and HY. Using H60 as a model antigen, we are investigating the cellular mechanisms of memory and tolerance of antigen-specific T cells.