Minor Histocompatibility Antigen (MiHA) (MiHA)

Minor Histocompatibility Antigens (MiHAs) are polymorphic peptides derived from intracellular proteins that are presented on the cell surface by Human Leukocyte Antigen (HLA) molecules (Bleakley & Riddell, 2004). In the context of allogeneic hematopoietic stem cell transplantation, donor-derived T-cell receptors (TCRs) recognize these MiHAs on leukemia cells when there is a genetic mismatch between the donor and recipient (Goulmy, 2006). This recognition is the molecular basis of the Graft-versus-Leukemia (GvL) effect, where donor T-cells selectively eliminate residual malignant cells (Griffioen et al., 2016). While MiHAs are the primary targets, donor TCRs may also recognize tumor-associated antigens (TAAs) that are overexpressed in leukemic blasts, such as WT1 or PRAME (Warren et al., 2017). Therapeutic strategies targeting these molecules include donor lymphocyte infusions (DLI) and the development of TCR-engineered T-cell therapies designed to enhance GvL while minimizing systemic toxicity (Spierings, 2014). The primary therapeutic challenge is the potential for Graft-versus-Host Disease (GvHD), which occurs if the targeted MiHA is also expressed on healthy recipient tissues (Hambach & Goulmy, 2005).

Other names

Leukemia cells recognized by donor T-cell receptorsMinor histocompatibility antigenmHagLeukemia-associated antigenGraft-versus-leukemia target

T-cell receptor-mediated recognition of specific peptide-MHC complexes on the surface of leukemia cells, leading to the activation of cytotoxic T-lymphocytes and subsequent granzyme/perforin-mediated lysis of the target cells.