Targeting alloreactive donor T-cells to hematopoietic system-restricted minor histocompatibility antigens to dissect graft-versus-leukemia effects from graft-versus-host disease after allogeneic stem cell transplantation.

The graft-versus-leukemia (GVL) effect of HLA-identical allogeneic stem cell transplantation is mainly mediated by alloreactive T-cells directed at the minor histocompatibility antigens (H ags) expressed on the leukemic cells of the recipient. Minor H ags are major histocompatibility complex-bound polymorphic peptides that are derived from intracellular proteins and that can show ubiquitous or hematopoietic system-restricted expression. Whereas ubiquitous minor H ags are involved both in the GVL effect and in graft-versus-host disease (GVHD), hematopoietic system-specific minor H ags expressed on leukemic cells are considered important targets for leukemia-specific cellular immunotherapy with a low risk of GVHD. This review will summarize the current knowledge of the immunobiology of minor H ags and discuss the advantages and drawbacks of cellular immunotherapy strategies that aim to separate the GVL effect from GVHD by targeting donor T-cells to hematopoietic system-specific minor H ags.