Minor histocompatibility antigen-Human Leukocyte Antigen complex (miHA-HLA)

The Minor histocompatibility antigen-Human Leukocyte Antigen (miHA-HLA) complex is a molecular target central to the immunology of allogeneic hematopoietic stem cell transplantation (allo-HSCT). These complexes consist of host-derived polymorphic peptides (miHAs) presented by HLA molecules on the surface of cells, including malignant ones (Goulmy, 1997). In a transplant setting, the donor's polyclonal T-cell receptor (TCR) repertoire recognizes these mismatched complexes as non-self, initiating a targeted immune response (Bleakley & Riddell, 2011). This recognition is the primary driver of the graft-versus-leukemia (GvL) effect, which is crucial for preventing cancer relapse by eliminating residual tumor cells. However, the expression of these miHAs on healthy recipient tissues can lead to graft-versus-host disease (GvHD), a significant cause of morbidity (Griffioen et al., 2016). Therapeutic interventions, such as donor lymphocyte infusions (DLI) or TCR-engineered T cells, aim to exploit this recognition to treat hematologic malignancies like leukemia and lymphoma while minimizing off-target effects (Warren et al., 2010). Modern research focuses on identifying lineage-restricted miHAs to improve the safety and efficacy of these immunotherapies.

Other names

Minor histocompatibility antigensmiHAmHAgMismatched HLA-peptide complexmiHA-MHC complex

T-cell mediated cytotoxicity following T-cell receptor (TCR) binding to the miHA-HLA complex, leading to the release of perforin and granzymes and induction of apoptosis in the target cell.