Human leukocyte antigen class I (HLA class I) (HLA-I)

Human leukocyte antigen class I (HLA class I) molecules are a group of cell surface glycoproteins, including HLA-A, HLA-B, and HLA-C, that are essential for the immune system's ability to distinguish self from non-self (Parham, 2005). These molecules serve as primary ligands for inhibitory killer-cell immunoglobulin-like receptors (KIRs) expressed on natural killer (NK) cells and some T cell subsets (Long, 2008). When an inhibitory KIR binds to its specific HLA class I ligand on a recipient cell, it sends a signal that prevents the NK cell from attacking, a process known as self-tolerance (Sivori et al., 2019). In clinical settings such as hematopoietic stem cell transplantation, the absence of a specific HLA ligand in the recipient that matches the donor's KIR (KIR-HLA mismatch) can lead to NK cell activation, which is exploited to eliminate residual leukemic cells—a phenomenon known as the graft-versus-leukemia effect (Ruggeri et al., 2002). Conversely, many tumors downregulate HLA class I expression to evade T cell detection, but this can make them susceptible to NK cell-mediated recognition (Sivori et al., 2019). Therapeutic agents like lirilumab are designed to block the interaction between inhibitory KIRs and HLA class I ligands, thereby enhancing the anti-tumor activity of NK cells in patients with various malignancies (Vey et al., 2012).

Other names

MHC class IMajor histocompatibility complex class IHLA-AHLA-BHLA-CInhibitory KIR ligands

Blockade of the inhibitory interaction between KIR receptors on effector cells and HLA class I ligands on target cells to enhance immune-mediated cytotoxicity.