Stress-induced ligands and antibody-coated cells (SIL/ACC)

This target entry describes a physiological state of diseased cells rather than a single molecular entity. It encompasses malignant or virally infected cells that have upregulated stress-induced ligands, such as MHC class I polypeptide-related sequence A/B (MICA/B) and UL16-binding proteins (ULBPs), which serve as 'eat-me' signals for the innate immune system. Additionally, it includes cells that have been opsonized by IgG antibodies, marking them for destruction via the Fc-gamma receptor IIIa (CD16) pathway. In a clinical context, these cells are the primary targets for Natural Killer (NK) cell-based therapies and monoclonal antibodies. The interaction involves the dual recognition of stress signals through the NKG2D receptor and antibody-coated surfaces through CD16, leading to the formation of an immunological synapse. This synergy triggers the release of perforins and granzymes, resulting in the targeted lysis of the abnormal cell. Understanding this target profile is critical for developing bispecific innate cell engagers and enhancing the efficacy of antibody-dependent cellular cytotoxicity (ADCC) in oncology and infectious disease treatments.

Other names

NKG2D ligandsMICA/B and ULBP expressing cellsADCC target cellsOpsonized target cellsStress-induced ligand-positive malignant cells

Therapeutic antibodies bind to specific antigens on the target cell surface, while their Fc region engages CD16 (FcγRIIIa) on NK cells to trigger ADCC. Simultaneously, stress-induced ligands (MICA/B, ULBPs) on malignant or infected cells bind to the NKG2D receptor on NK cells and T cells, providing co-stimulatory signals that enhance cytolytic activity and cytokine production to eliminate the target cell.