Moesin: A novel receptor on NK lymphocytes binds to TOMM40 on K562 leukemia cells initiating cytolysis

Abstract

Natural killer lymphocytes (NK cells) are the first line of defense (innate immunity) against viral infections and leukemia since they do not require activation to deliver a lethal hit to infected/aberrant cells. In contrast, T lymphocytes require stimulation by a foreign/neo - antigen, which may take days before they are active against the pathogen (adaptive immunity). A number of receptors on activated NK cells that kill the prototypical leukemia target cell line, K562, have been identified. To date, the receptor(s) by which freshly isolated unstimulated NK cells (naïve, nNK) kill K562 has not been fully elucidated. We provide peptide sequence and immune-blot data from ligand pull down experiments that moesin, a protein that typically links the inner leaf of the plasma membrane to the cytoskeleton, additionally, in NK cells, localizes to the cell surface where it may bind to its ligand, TOMM40 (aka Haymaker, HYMKR), on leukemia cells thereby initiating their destruction. Flow cytometry experiments with a mouse monoclonal antibody (Mab) to a moesin peptide (554 to 565) were performed. Moesin was detected on the surface of CD3^-, CD16⁺nNK cells but was not detected on the surface of freshly isolated unstimulated CD3⁺, CD16^- T cells or CD19⁺, CD16^- B cells from healthy subjects. Moesin, is therefore another marker that distinguishes unstimulated CD3^-, CD16⁺ NK cells from other non-activated lymphocytes. The anti -moesin peptide Mab was highly effective (>95% inhibition) in blocking target cell cytolysis by CD16⁺ lymphocytes demonstrating that moesin-HYMKR interaction appears to be necessary for most of the observed cell death of K562 caused by unstimulated NK cells.

Keywords: Cytotoxicity; Haymaker; K562 leukemia cells; Moesin; Natural killer cells; TOMM40.