Killer immunoglobulin-like receptor (KIR) (KIR)

Killer immunoglobulin-like receptors (KIRs) are a diverse family of cell surface glycoproteins expressed primarily on Natural Killer (NK) cells and a subset of T cells (UniProt, 2024). They play a critical role in regulating the immune response by interacting with Major Histocompatibility Complex (MHC) class I molecules, specifically Human Leukocyte Antigen (HLA) in humans, on target cells (Purdy & Campbell, 2009). KIRs can be either inhibitory or activating; inhibitory KIRs recognize self-HLA molecules to prevent autoimmunity, while the absence of these ligands (missing-self) or the presence of activating signals triggers NK cell-mediated lysis (Purdy & Campbell, 2009). In the context of adoptive immunotherapy, NK cells expanded using membrane-bound Interleukin-21 (mbIL21) exhibit significantly enhanced proliferation and cytotoxic potential compared to other expansion methods (Denman et al., 2012). Therapeutic strategies often involve blocking inhibitory KIRs with monoclonal antibodies, such as lirilumab, to disrupt the inhibitory signaling and enhance anti-tumor activity against malignancies that express KIR ligands (ClinicalTrials.gov, 2024). This approach is particularly relevant in treating hematologic malignancies and certain solid tumors where tumor cells evade T-cell recognition by downregulating HLA or expressing inhibitory ligands (Purdy & Campbell, 2009).

Other names

CD158Killer cell immunoglobulin-like receptorsKIR familyKIRs

Blockade of inhibitory KIR receptors to prevent the suppression of Natural Killer (NK) cell activity, thereby enhancing the lysis of tumor cells that express KIR ligands.