A significant share of allogeneic hematopoietic stem cell
transplantations (allo-HSCT) results in the relapse of malignant disease. The T cell immune response to
minor histocompatibility antigens (MiHAs) promotes a favorable graft-versus-
leukemia response. The immunogenic
MiHA HA-1 is a promising target for
leukemia immunotherapy, as it is predominantly expressed in hematopoietic tissues and presented by the common
HLA A*02:01 allele. Adoptive transfer of HA-1-specific modified CD8+ T cells could
complement allo-HSCT from HA-1- donors to HA-1+ recipients. Using bioinformatic analysis and a reporter T cell line, we discovered 13
T cell receptors (TCRs) specific for HA-1. Their affinities were measured by the response of the TCR-transduced reporter cell lines to HA-1+ cells. The studied TCRs showed no cross-reactivity to the panel of donor peripheral mononuclear blood cells with 28 common HLA alleles. CD8+ T cells after endogenous TCR knock out and introduction of transgenic HA-1-specific TCR were able to lyse hematopoietic cells from HA-1+ patients with acute myeloid, T-, and
B-cell lymphocytic leukemia (n = 15). No cytotoxic effect was observed on cells from HA-1- or
HLA-A*02-negative donors (n = 10). The results support the use of HA-1 as a target for post-transplant T cell
therapy.