Mismatched Histocompatibility Antigens (MHC/mHag)

Mismatched histocompatibility antigens represent the primary immunological targets in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and donor lymphocyte infusion (DLI). These targets consist of Major Histocompatibility Complex (MHC/HLA) molecules or Minor Histocompatibility Antigens (mHags), which are polymorphic peptides derived from cellular proteins that differ between the donor and the recipient (Goulmy, 1997). When recipient malignant cells present these mismatched antigens on their surface, they are recognized as non-self by donor-derived T cells (Bleakley & Riddell, 2004). This recognition initiates the Graft-versus-Leukemia (GvL) effect, a therapeutic immune response that eliminates residual cancer cells through cytotoxic T-lymphocyte activity (Appelbaum, 2001). However, because these antigens may also be expressed on healthy recipient tissues, their targeting is the fundamental cause of Graft-versus-Host Disease (GvHD). Modern therapeutic strategies, such as TCR-engineered T cells, aim to specifically target mHags with restricted expression to hematopoietic lineages to maximize GvL while minimizing GvHD (Warren et al., 2017).

Other names

Minor histocompatibility antigensMajor histocompatibility antigensAllogeneic antigensmHagsHLA-mismatched antigensGraft-versus-leukemia targetsRecipient-specific antigens

Donor-derived T cells recognize mismatched antigens presented on the surface of recipient malignant cells, leading to T-cell activation, secretion of cytotoxic granules such as perforin and granzyme, and induction of apoptosis in the target cells, a process known as the Graft-versus-Leukemia (GvL) effect.