Minor histocompatibility antigen peptide-Major Histocompatibility Complex (mHag-MHC complex)

Minor histocompatibility antigen (mHag) peptide-Major Histocompatibility Complex (MHC) complexes are cell-surface targets composed of polymorphic peptides derived from intracellular proteins presented by MHC molecules [1, 24]. These complexes are critical in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT), where they are recognized by donor T cells as foreign antigens, leading to either beneficial graft-versus-leukemia (GVL) effects or detrimental graft-versus-host disease (GVHD) [17, 26]. Therapeutic targeting of these complexes, particularly those restricted to hematopoietic cells like HA-1, allows for the selective elimination of malignant cells while sparing non-hematopoietic tissues [8, 13]. Current drug development focuses on T-cell receptor-engineered T-cell (TCR-T) therapies, such as BSB-1001 and PRO TCR-401, which are designed to recognize specific mHag-MHC combinations to treat relapsed or refractory leukemias [15, 18, 23]. These therapies leverage the high specificity of TCRs for peptide-MHC ligands to provide a potent and targeted anti-tumor response [4, 33]. Additionally, TCR-mimic antibodies and peptide vaccines are being explored to enhance the immune system's ability to detect these specific complexes [4, 31]. The success of these treatments depends on precise patient selection based on HLA typing and mHag genotyping to ensure the presence of the target complex on tumor cells [21, 30].

Other names

Minor histocompatibility antigen (mHag) peptide-MHC complexpMHC complexHLA-peptide complexMinor H antigen-MHC complexMiHA-HLA complexPeptide-MHC complex

T-cell redirection and activation through specific recognition of peptide-MHC complexes, leading to targeted cytotoxicity against cells expressing the antigen.