Leukemia-associated peptide-HLA complex (pHLA/allo-HLA)

Host leukemia peptide–HLA complexes and allogeneic HLA molecules represent the primary immunological targets of the graft-versus-leukemia (GvL) effect following allogeneic hematopoietic stem cell transplantation (allo-HSCT). These targets consist of peptides derived from leukemia-associated antigens (LAAs) or minor histocompatibility antigens (mHags) presented on the surface of malignant cells by Human Leukocyte Antigen (HLA) molecules (PMID: 28637614). In the context of transplantation, donor-derived T cells recognize these complexes as foreign or abnormal, leading to the targeted elimination of residual leukemia cells. Additionally, in HLA-mismatched settings, the allogeneic HLA molecules themselves can serve as direct targets for donor T-cell recognition. Therapeutic strategies leveraging these targets include donor lymphocyte infusions (DLI) and advanced adoptive T-cell therapies, such as TCR-engineered T cells designed to recognize specific peptide-HLA combinations like WT1 or PRAME (PMID: 30552148). While these interactions are essential for eradicating disease, they also pose a significant risk of graft-versus-host disease (GvHD) if the targeted antigens are expressed on healthy host tissues (PMID: 11090071). Consequently, the identification of highly leukemia-specific peptide-HLA combinations is a critical focus for improving the safety and efficacy of immunotherapy in hematologic malignancies.

Other names

Host leukemia peptide-HLA complexMinor histocompatibility antigen-HLA complexmHag-HLA complexLeukemia-associated antigen-HLA complexAllo-HLAMHC-peptide complex

T-cell receptor (TCR) mediated recognition of peptide-HLA complexes or allogeneic HLA molecules, leading to cytotoxic T-lymphocyte activation and targeted lysis of leukemia cells.