Human leukocyte antigen (HLA) genes and transplant-associated genomic loci (HLA)

The Human Leukocyte Antigen (HLA) genes and associated genomic loci constitute the Major Histocompatibility Complex (MHC) in humans, located on chromosome 6 (NIH, 2023). These DNA sequences encode cell-surface proteins essential for the adaptive immune system to distinguish between self and non-self by presenting peptide antigens to T-cells (Janeway's Immunobiology, 2017). In the context of transplantation, the high polymorphism of these loci is the primary barrier to successful engraftment, as mismatches trigger T-cell mediated rejection or graft-versus-host disease (GVHD) (Nature Reviews Immunology, 2018). While the DNA sequences themselves are not traditional pharmacological targets for small molecules, they serve as critical biomarkers for donor-recipient matching and risk stratification (Blood, 2021). Emerging therapies, such as CRISPR-based gene editing, aim to modify these sequences to create "universal" donor cells by knocking out HLA expression to evade immune detection (Science Translational Medicine, 2020). Additionally, specific HLA alleles are strongly associated with adverse drug reactions, such as HLA-B*57:01 and abacavir hypersensitivity, making these genomic loci vital for pharmacogenomic screening (CPIC, 2021).

Other names

Major Histocompatibility ComplexMHCHLA complexHuman leukocyte antigen systemTransplant-associated genomic loci

Immunological matching for transplantation and pharmacogenomic screening for drug hypersensitivity.