Minor histocompatibility antigen (mHAg) peptides presented by HLA class II molecules (mHAg-HLA-II)

Minor histocompatibility antigens (mHAgs) are peptides derived from polymorphic proteins that differ between a stem cell donor and a transplant recipient [1]. When these peptides are presented by HLA class II molecules on the surface of recipient hematopoietic and malignant cells, they serve as specific targets for donor-derived CD4+ T cells [2]. This interaction is a primary driver of the graft-versus-leukemia (GvL) effect, which is essential for eliminating residual malignant cells after allogeneic hematopoietic stem cell transplantation [3]. Because HLA class II expression is predominantly restricted to hematopoietic cells and professional antigen-presenting cells, targeting these mHAgs can potentially induce GvL without triggering systemic graft-versus-host disease (GvHD) in non-hematopoietic tissues [4]. Therapeutic approaches targeting these complexes include donor lymphocyte infusions, the administration of ex vivo expanded mHAg-specific T cells, and the development of T-cell receptor (TCR) gene therapies [3]. Identifying and characterizing these antigens is critical for personalizing immunotherapy and improving outcomes in patients with hematologic malignancies [4].

Other names

Minor histocompatibility antigensmHAgHematopoietic-restricted minor histocompatibility antigensmHAg-MHC II complexesMinor histocompatibility antigen peptides presented by HLA class II molecules on recipient hematopoietic and malignant cells

Recognition of the peptide-MHC complex by donor-derived T-cell receptors (TCRs), leading to the activation of cytotoxic and helper T-cell responses against malignant cells [2][3].