Role of integrin receptors in cytotoxic lymphocyte function
Natural killer cells (NK cells) are an essential tool of the immune cell defense against aberrant cells, especially tumors. NK cells can kill tumor target cells upon activation through one of the germ-line coded activating receptors, CD16 in particular. CD16 recognizes Fc fragments of IgG antibody molecules bound to antigens on the surface of the target cell and mediates target cell lysis in the process called ADCC (antibody dependent cellular cytotoxicity). The killing of the target cell is mediated by the release of soluble molecules contained within membrane bound vesicles, lytic granules. The granules are released directionally from the NK cell to the target cell through highly organized contact interface called the immunological synapse (IS) as a result of a complex series of signaling events. In the current work we examine the range of integrin employed by NK cells and address the contribution of integrin outside in signaling to effective CD16-mediated NK cytotoxicity. We found that for their activation NK cells utilize a wide range of integrin molecules, both containing and not containing beta2 subunit. We also found that integrin engagement supports sustained proximal signaling and extended adhesion area formation. Furthermore, we show that integrin-mediated signaling and not the amount of available CD16 ligands is primarily responsible for size, mobility and persistence of CD16 microclusters. The finding described herein uncover novel mechanisms used by NK cells to mediate efficient cytotoxic response under wide range of conditions and demonstrate the crucial importance of integrin involvement in NK cell signal transduction. These findings have important implications for the development of personalized anti-tumor therapies in the future.
Molecular biology|Cellular biology|Immunology
Steblyanko, Maria A, "Role of integrin receptors in cytotoxic lymphocyte function" (2014). ETD Collection for Thomas Jefferson University. AAI3705046.