Minor Histocompatibility Antigens in Hematopoietic Stem Cell Transplantation

Minor histocompatibility antigens (MiHAs) are polymorphic peptides derived from genetic differences between donor and recipient and presented by HLA molecules on the surface of cells. In HLA-matched allogeneic hematopoietic stem cell transplantation (HSCT), donor T cells recognise MiHAs as foreign, triggering beneficial graft-versus-leukaemia (GvL) responses against residual malignant cells but also potentially harmful graft-versus-host disease (GvHD) when normal tissues are targeted. MiHAs may be ubiquitously expressed or restricted to haematopoietic lineages; the former contribute to both GvL and GvHD, while the latter can mediate selective GvL without widespread tissue damage. Advances in genomic sequencing, immunopeptidomics and bioinformatic prediction have expanded the known MiHA repertoire, revealing hundreds of peptide candidates. Identification of immunodominant and haematopoietic-restricted MiHAs has informed strategies for graft engineering, donor selection and adoptive T cell therapies aimed at maximising anti-leukaemic efficacy while limiting toxicity. These developments underpin efforts to tailor HSCT and post-transplant immunotherapies on the basis of individual MiHA profiles, with the ultimate goal of improving patient outcomes through precision transplantation immunology.

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Minor Histocompatibility Antigens in Hematopoietic Stem Cell Transplantation publication trend

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Technical terms

Minor histocompatibility antigen (MiHA): A peptide derived from a polymorphic protein that differs between donor and recipient and is presented by HLA molecules to T cells.

Hematopoietic stem cell transplantation (HSCT): A procedure in which a patient’s diseased blood and immune system is replaced with healthy donor haematopoietic stem cells.

Graft-versus-leukaemia (GvL) effect: The beneficial immune response in which donor T cells eliminate residual malignant cells after transplantation.

Graft-versus-host disease (GvHD): A complication of allogeneic transplantation in which donor T cells attack healthy recipient tissues.

HLA molecules: Human leukocyte antigen proteins that present peptides, including MiHAs, on cell surfaces for recognition by T cells.

References

1. Autosomal Minor Histocompatibility Antigens: How Genetic Variants Create Diversity in Immune Targets. Frontiers in Immunology (2016).
2. Minor Histocompatibility Antigen-Specific T Cells. Frontiers in Pediatrics (2020).
3. Minor histocompatibility antigens to predict, monitor or manipulate GvL and GvHD after allogeneic hematopoietic cell transplantation. Best Practice & Research Clinical Haematology (2024).
4. In Silico Analysis of the Minor Histocompatibility Antigen Landscape Based on the 1000 Genomes Project. Frontiers in Immunology (2018).