Peptide-Major Histocompatibility Complex presenting leukemia-associated antigens (pMHC-LAA)

Peptide-Major Histocompatibility Complexes (pMHCs) presenting leukemia-associated antigens (LAAs) are specialized molecular structures on the surface of hematopoietic and leukemic cells that serve as primary targets for T-cell-mediated immunity. These complexes are formed when intracellularly processed peptides, derived from minor histocompatibility antigens (MiHAs) or tumor-associated antigens (TAAs), are loaded onto Major Histocompatibility Complex (MHC) molecules, such as Human Leukocyte Antigen (HLA) class I or II [1, 9]. In the context of leukemia, these pMHCs are crucial for the graft-versus-leukemia (GVL) effect, where donor T cells recognize recipient-specific antigens following allogeneic hematopoietic stem cell transplantation [2, 7]. Therapeutic interventions, including TCR-engineered T cells (TCR-T), TCR-like antibodies, and bispecific T-cell engagers, are designed to bind these specific pMHC epitopes with high affinity to trigger potent anti-leukemic cytotoxicity [4, 14]. Common antigenic targets within these complexes include Wilms Tumor 1 (WT1), PRAME, and HA-1, which exhibit restricted or elevated expression in malignant cells [1, 6]. Despite their therapeutic potential, challenges such as HLA down-regulation by tumor cells and the risk of off-target toxicity to healthy hematopoietic tissues or graft-versus-host disease (GVHD) remain significant clinical concerns [4, 19].

Other names

pMHC-leukemia antigen complexMiHA-MHC complexTAA-MHC complexHLA-peptide complexLeukemia-associated antigen pMHCpMHC-MiHA complex

T-cell receptor binding and activation