Leukemia-associated peptide-MHC complex (LAA-MHC)

The leukemia-associated peptide-MHC complex is a molecular target on the surface of leukemic cells consisting of a specific peptide antigen bound to a major histocompatibility complex (MHC) molecule. These antigens include minor histocompatibility antigens (mHags), which arise from genetic polymorphisms between a transplant donor and recipient, and leukemia-associated antigens (LAAs), which are proteins overexpressed or mutated in malignant cells. In the context of allogeneic hematopoietic stem cell transplantation, these complexes are recognized by donor-derived T-cell receptors (TCRs), triggering the graft-versus-leukemia (GvL) effect. This immune response is critical for eradicating residual disease and preventing relapse in patients with hematologic malignancies. Therapeutic interventions targeting these complexes include donor lymphocyte infusions (DLI), which provide a broad repertoire of donor T cells, and more specific approaches like peptide vaccines and TCR-engineered T-cell therapies. Specific antigens such as WT1, PRAME, and various mHags (e.g., HA-1) have been identified as potent targets for these therapies. A significant challenge in targeting these antigens is the potential for graft-versus-host disease (GvHD), which occurs if the targeted antigens are also expressed on healthy recipient tissues. Ongoing research focuses on identifying antigens with expression restricted to the hematopoietic system to maximize GvL while minimizing GvHD.

Other names

Minor histocompatibility antigen (mHag)Leukemia-associated antigen (LAA)Graft-versus-leukemia targetMinor H antigenMiHAPeptide-HLA complexpMHC complex

T-cell mediated cytotoxicity