NK cell activating and adhesion ligands (ICAM-1, CD155, CD112, CD48)

This target group consists of several surface proteins on target cells—specifically ICAM-1, CD155 (PVR), CD112 (Nectin-2), and CD48—that are recognized by the activating and adhesion receptors LFA-1, DNAM-1, and 2B4 on Natural Killer (NK) cells. ICAM-1 (CD54) is a member of the immunoglobulin superfamily that binds to the integrin LFA-1 (CD11a/CD18), a process essential for the formation and stabilization of the immunological synapse between the NK cell and its target (PubMed: 10891884). CD155 and CD112 serve as ligands for the DNAM-1 (CD226) receptor, providing critical activating signals that trigger NK cell cytotoxicity and are often upregulated in response to cellular stress or malignant transformation (PubMed: 15905547). CD48 (SLAMF2) interacts with the 2B4 (CD244) receptor, acting as a coreceptor to enhance the lytic activity and interferon-gamma production of NK cells (PubMed: 11714777). In the context of adoptive immunotherapy using infused NK cells or CAR-NK cells, these ligands are vital for the recognition and elimination of tumor cells. However, tumors often employ evasion strategies such as the downregulation of these ligands or the expression of competing inhibitory receptors, such as TIGIT, which can impair the efficacy of NK cell-based therapies.

Other names

Intercellular adhesion molecule 1Poliovirus receptorNectin-2SLAM family member 2CD54CD155CD112CD48PVRPVRL2SLAMF2NK cell activating ligands

Engagement of these ligands by their respective receptors (LFA-1, DNAM-1, and 2B4) on NK cells promotes the formation of the immunological synapse and triggers the release of cytotoxic granules and pro-inflammatory cytokines.