Human leukocyte antigen-mismatched recipient leukemic and hematopoietic cells (HLA-mismatched cells)

Human leukocyte antigen-mismatched recipient leukemic and hematopoietic cells represent the primary cellular targets in allogeneic hematopoietic stem cell transplantation and adoptive cellular immunotherapies (Appelbaum, 2001). These cells are identified by the donor immune system through disparities in the Human Leukocyte Antigen (HLA) complex, which serves as the major histocompatibility complex in humans. When donor-derived T cells or Natural Killer (NK) cells encounter these mismatched cells, they recognize them as foreign, triggering a potent cytotoxic response (Ruggeri et al., 2002). This biological interaction is the foundation of the Graft-versus-Leukemia (GvL) effect, which is intended to eliminate residual cancer cells following a transplant. However, because these mismatched antigens are also present on healthy recipient hematopoietic cells and other tissues, this process can lead to Graft-versus-Host Disease (GvHD) (Zeiser & Blazar, 2017). Drugs and therapeutic interventions, such as donor lymphocyte infusions or post-transplant cyclophosphamide, are used to modulate this immune response (Luznik et al., 2008). The goal of targeting these cells is to achieve a balance where the malignancy is eradicated while the recipient's healthy organs are spared from immune attack.

Other names

Allogeneic recipient cellsHLA-disparate host cellsMismatched hematopoietic cellsNon-self leukemic cells

Recognition of mismatched HLA class I or II molecules by donor T-cell receptors or the absence of self-MHC ligands for donor NK-cell inhibitory receptors, leading to targeted cytolysis of recipient cells (Ruggeri et al., 2002; Zeiser & Blazar, 2017).