Minor histocompatibility antigen peptide–HLA complex (mHAg-HLA complex)

Minor histocompatibility antigen (mHAg) peptide–HLA complexes are molecular targets formed when polymorphic peptides, derived from proteins that differ between individuals, are presented by Human Leukocyte Antigen (HLA) molecules on the cell surface (Goulmy, 1997). In the context of allogeneic hematopoietic stem cell transplantation, these complexes are recognized by donor-derived T cells as foreign, triggering a potent immune response (Bleakley & Riddell, 2011). When these mHags are expressed specifically on hematopoietic and leukemic cells, they facilitate the graft-versus-leukemia (GVL) effect, allowing for the targeted destruction of malignant cells (Griffioen et al., 2016). However, if the mHag is also expressed in non-hematopoietic tissues, it can lead to the serious complication of graft-versus-host disease (GVHD) (Spierings, 2014). Therapeutic development focuses on identifying hematopoietic-restricted mHags, such as HA-1, to create TCR-engineered T cells or TCR-like antibodies that can selectively eliminate leukemia without damaging healthy organs (Medigene, 2021). These complexes represent a precision medicine approach to immunotherapy, requiring specific HLA-matching and genetic screening of both donor and recipient to ensure efficacy and safety (Warren et al., 2017).

Other names

mHAgMinor histocompatibility antigenmHAg-MHC complexHematopoietic-restricted minor histocompatibility antigenMinor histocompatibility antigen peptide–HLA class I/II complexes on hematopoietic and leukemic cells

T-cell receptor binding and subsequent activation of cytotoxic T-lymphocytes to induce apoptosis in target cells expressing the specific peptide-HLA complex.