Minor histocompatibility antigen–HLA complex (mHAg-HLA complex)

Minor histocompatibility antigen (mHAg)–HLA complexes are formed when peptides derived from polymorphic proteins, which differ between individuals, are presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (PubMed: 10583913). In the context of allogeneic hematopoietic stem cell transplantation, these complexes serve as critical targets for the donor immune system to recognize and eliminate residual leukemic cells, a phenomenon known as the graft-versus-leukemia (GvL) effect (NIH: National Cancer Institute). When the target mHAg is exclusively expressed on hematopoietic cells, such as the HA-1 or HA-2 antigens, it allows for a therapeutic window where donor T cells can eradicate the cancer without attacking non-hematopoietic tissues, thereby minimizing the risk of systemic graft-versus-host disease (GvHD) (PubMed: 21670456). Therapeutic strategies currently under development include the use of donor lymphocyte infusions, TCR-engineered T cells, and TCR-like monoclonal antibodies designed to specifically bind these peptide-MHC combinations (PubMed: 30206112). These targets are particularly valuable for treating relapsed leukemia after transplantation by focusing the immune response on the recipient's hematopoietic lineage while sparing vital organs.

Other names

Minor histocompatibility antigenmHAgMinor H antigenmHAg-MHC complexHematopoietic-restricted minor histocompatibility antigenLineage-specific minor histocompatibility antigen

Targeting of specific peptide-HLA complexes by T-cell receptors (TCRs) or TCR-like antibodies to induce selective lysis of cells expressing the minor histocompatibility antigen.