Characterization and recognition of minor histocompatibility antigens

Abstract

Minor histocompatibility antigens (MiHA) are structures that can be recognized by T cells. In the setting of allogeneic stem cell transplantation MiHA presented by patient cells can be recognized by donor T cells. If MiHA that are targeted by donor T cells are selectively expressed by leukemic cells, beneficial graft-versus-leukemia reactivity can be observed. However, if MiHA are presented by normal tissue cells, graft-versus-host disease can be a serious complication. The thesis describes methods that were applied to characterize the molecular structure of MiHA. T cells that recognized MiHA recognized on malignant hematopoietic and solid tumor cells were identified. MiHA recognition on both normal and malignant cells was measured. We finally investigated the differences of the donor T cell response of patients with a clinical graft-versus-leukemia reactivity who did or did not develop graft-versus-host disease.