Minor histocompatibility antigens (mHags) (mHag)

Minor histocompatibility antigens (mHags) are polymorphic peptides derived from host proteins that differ between a transplant donor and recipient due to genetic variations, such as single nucleotide polymorphisms (SNPs) [1.3.2]. These peptides are processed and presented by recipient Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA) molecules on the cell surface, where they can be recognized by donor-derived T cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT) [1.5.3]. While many mHags are ubiquitously expressed and contribute to graft-versus-host disease (GvHD), a subset of mHags is restricted to the hematopoietic lineage, including leukemia cells [1.3.1, 1.4.1]. These hematopoietic-restricted mHags, such as HA-1 and ACC-1, serve as ideal targets for immunotherapy because they allow donor T cells to selectively eliminate residual malignant cells (graft-versus-leukemia effect) without attacking non-hematopoietic tissues [1.2.1, 1.5.1]. Therapeutic approaches targeting these antigens include donor lymphocyte infusions, peptide vaccines, and engineered T-cell receptor (TCR-T) therapies, such as MDG1021, which are currently being evaluated in clinical trials to prevent or treat leukemia relapse post-transplant [1.5.2, 1.5.4]. The clinical utility of these targets is currently limited by the requirement for specific HLA-restricting alleles and the presence of the relevant genetic polymorphism in the recipient but not the donor [1.3.3, 1.5.1]. Safety concerns include the potential for off-target effects if the antigen is not strictly restricted to the hematopoietic system, as well as the risk of prolonged marrow aplasia [1.3.2, 1.5.2]. Despite these challenges, mHags remain a promising class of targets for precision immunotherapy in the context of hematological malignancies [1.3.4].

Other names

MiHAMinor H antigensHematopoietic-restricted minor histocompatibility antigensLeukemia-associated minor histocompatibility antigens

Adoptive T-cell therapy targeting peptide-HLA complexes; Peptide vaccination to induce antigen-specific T-cell responses; Donor lymphocyte infusion to provide alloreactive T cells.