Natural T-cell responses against minor histocompatibility antigen (mHag) HY following HLA-matched hematopoietic cell transplantation: what are the requirements for a ‘good’ mHag?

Abstract

Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative treatment modality for several hematologic malignancies. Conventional myeloablative conditioning regimens are associated with high treatment-related mortality. To this end, the introduction of nonmyeloablative (NMA) conditioning implies that older and more frail patients can be offered HCT, and recent data suggest comparable outcome of conventional and NMA–HCT, both with regards to efficacy and side effects, at least for selected indications.1 The curative principle in allogeneic HCT with NMA conditioning is solely related to the graft-versus-leukemia (GVL) effect, and several lines of evidence strongly suggest that donor T cells are the main effectors. In human leukocyte antigen (HLA), identical sibling HCT, T-cell responses to minor histocompatibility antigens (mHags) are—at least in part—responsible for the GVL effect but also cause graft-versus-host disease (GVHD). GVHD represents a major side effect of HCT, and it is well established that there exists correspondence between the GVL effect and GVHD. As a consequence, increased knowledge concerning mechanisms at play and the targets recognized may set the stage for development of treatment strategies that focus on induction of GVL in the absence of GVHD.2 Obviously, increased insight into the cells, molecules and antigens involved with GVL and GVHD are important to possibly be able to control and direct these events more precisely.