Minor histocompatibility antigens as targets for T-cell therapy after bone marrow transplantation

In allogeneic bone marrow transplantation, differences between donor and recipient at minor histocompatibility loci, which encode allelic proteins containing variant peptide sequences, may result in adverse immune reactions such as graft-versus-host disease (GVHD), or graft rejection, but also a beneficial graft versus leukemia (GVL) response. Some minor H antigens are restricted in their expression to hematopoietic cells, including leukemic progenitors, suggesting it may be possible to separate GVHD and GVL responses. The antigenic peptides for a few human minor H antigens have been identified, and efforts to identify the genes encoding minor H antigens are being pursued. These advances promise to provide a more detailed understanding of the immunobiology and pathogenesis of GVHD and GVL responses and opportunities to selectively augment T-cell responses that promote a GVL effect by adoptive immunotherapy with T-cell clones specific for defined minor H determinants.