Mismatched Human Leukocyte Antigens and minor Histocompatibility Antigens (HLA/mHAg)

Host immune cells expressing mismatched Human Leukocyte Antigens (HLA) or minor Histocompatibility Antigens (mHAg) serve as the primary immunological targets following allogeneic hematopoietic stem cell transplantation. HLA molecules are highly polymorphic cell surface glycoproteins responsible for presenting peptides to T cells, while mHAgs are polymorphic self-proteins that differ between donor and recipient (Zeiser & Blazar, 2017, NEJM). When donor T cells encounter these mismatched antigens on host cells, they recognize them as foreign, triggering an alloreactive immune response. This interaction is the fundamental driver of Graft-versus-Host Disease (GvHD), where donor T cells attack host tissues, but it also facilitates the Graft-versus-Leukemia (GvL) effect, where donor cells eliminate residual malignant host cells (Mehta et al., 2021, StatPearls). Therapeutic strategies involve either suppressing the donor T-cell response using drugs like calcineurin inhibitors or selectively targeting specific mHAgs to enhance GvL without inducing systemic GvHD (Ferrara et al., 2009, Lancet). Understanding the specific HLA and mHAg profiles is critical for donor selection and managing post-transplant complications.

Other names

Allogeneic host antigensMismatched MHCMinor histocompatibility antigensHost antigen-presenting cellsAllogeneic HLA complexes

Immunosuppressive agents inhibit the activation, signaling, or proliferation of donor T cells that recognize mismatched host HLA or mHAg complexes. Targeted cellular therapies, such as TCR-engineered T cells, may specifically bind these mismatched peptide-MHC complexes to induce targeted cell lysis.