Host normal tissues expressing mismatched HLA and minor histocompatibility antigens

Host normal tissues expressing mismatched human leukocyte antigens (HLA) and minor histocompatibility antigens (mHAs) represent the biological targets of donor-derived immune cells in graft-versus-host disease (GvHD) (Source: NIH). In the setting of allogeneic hematopoietic stem cell transplantation, donor T cells recognize these polymorphic host antigens as non-self, leading to an orchestrated immune attack against healthy tissues (Source: PubMed, PMID: 28231465). The primary organs affected are the skin, gastrointestinal tract, and liver, where antigen-presenting cells display these mismatched peptides to donor CD4+ and CD8+ T cells (Source: PubMed, PMID: 30231154). While these tissues are the targets of the disease process, therapeutic intervention focuses on the donor immune system rather than the host tissues themselves. Drugs such as calcineurin inhibitors, JAK inhibitors, and BTK inhibitors are employed to suppress the activation and effector functions of the donor T cells, thereby protecting the host tissues from immune-mediated damage (Source: FDA). Monitoring HLA compatibility and specific mHA mismatches is essential for assessing GvHD risk and guiding prophylactic and therapeutic strategies (Source: NIH).

Other names

GvHD target tissuesAlloantigen-expressing host cellsHost minor histocompatibility antigensMismatched HLA-expressing tissuesAlloantigens

Inhibition of donor T-cell activation, proliferation, and cytokine production to prevent the recognition and destruction of host tissues expressing mismatched antigens (Source: FDA, PubMed).