Minor histocompatibility antigen-peptide–HLA class I complex (mHag-HLA class I complex)

Minor histocompatibility antigen (mHag)-derived peptide–HLA class I complexes are immunological targets formed by the presentation of polymorphic host peptides on HLA class I molecules (Bleakley & Riddell, 2011, Nature Reviews Cancer). These complexes are particularly significant in allogeneic hematopoietic stem cell transplantation (HSCT), where they serve as the primary targets for donor-derived T cells. When the mHag is expressed exclusively on hematopoietic cells, including malignant cells like those in leukemia or lymphoma, it facilitates a targeted Graft-versus-Leukemia (GvL) effect without inducing systemic Graft-versus-Host Disease (GvHD) (Goulmy et al., 1996, Science). Therapeutic interventions, such as TCR-engineered T cells and peptide-based vaccines, are designed to exploit this specificity to eradicate residual disease in patients with hematological malignancies (Griffioen et al., 2016, Blood). The efficacy of these treatments depends on the mismatch between donor and recipient genotypes and the restricted expression profile of the source protein (Spierings et al., 2003, Blood). This precision medicine approach aims to provide a potent anti-tumor response while maintaining a favorable safety profile by avoiding non-hematopoietic tissues.

Other names

Minor histocompatibility antigen-derived peptide–HLA class I complexes on recipient hematopoietic and malignant cellsmHag-MHC class I complexMinor histocompatibility antigensMiHA-HLA complexesHematopoietic-restricted minor histocompatibility antigenspMHC complex

Recognition of the specific peptide-HLA complex by the T-cell receptor (TCR) of donor-derived CD8+ cytotoxic T lymphocytes, leading to the targeted lysis of recipient hematopoietic and malignant cells (Bleakley & Riddell, 2011).