Human leukocyte antigen (HLA) class I and II mismatch (HLA mismatch)

Human leukocyte antigen (HLA) class I and II molecules are essential cell surface receptors that present antigenic peptides to T-cells, facilitating the immune system's discrimination between self and non-self [1]. In the context of allogeneic hematopoietic stem cell transplantation (HSCT), a mismatch between the HLA alleles of the donor and the recipient serves as the primary trigger for immune-mediated complications [2]. When donor immune effector cells, particularly T-cells, encounter mismatched HLA molecules on recipient tissues, they initiate a systemic inflammatory response known as Graft-versus-Host Disease (GvHD) [2, 3]. Conversely, recipient immune cells may recognize donor HLA as foreign, leading to graft rejection or failure [3]. Therapeutic interventions aim to manage this mismatch through pharmacological immunosuppression, such as calcineurin inhibitors, or through advanced cellular engineering techniques that selectively deplete or modulate specific T-cell subsets [4, 5]. Balancing the risks of GvHD against the beneficial graft-versus-leukemia (GvL) effect remains a central challenge in treating hematologic malignancies using mismatched donors [2]. Sources: [1] UniProt (HLA-A, HLA-B, HLA-DRB1); [2] StatPearls (Graft Versus Host Disease); [3] NIH/NCI (Hematopoietic Stem Cell Transplantation); [4] FDA (Prograf/Tacrolimus Label); [5] Orca Bio (Orca-T Clinical Pipeline).

Other names

HLA incompatibilityMHC mismatchAllogeneic HLA disparityDonor-recipient HLA mismatchMajor histocompatibility complex mismatch

Calcineurin inhibition, T-cell depletion, T-cell costimulation blockade, Selective T-cell subset modulation, DNA synthesis inhibition, and regulatory T-cell enrichment.