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

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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 anti-genic 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.

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