Cell Surface-Expressed Moesin-Like Receptor Regulates T Cell Interactions with Tissue Components and Binds an Adhesion-Modulating IL-2 Peptide Generated by Elastase

Abstract

The adhesion of leukocytes to the extracellular matrix (ECM) depends on their responses to variations in the chemotactic signals in their milieu, as well as on the functioning of cytoskeletal and context-specific receptors. Ezrin, radixin, and moesin constitute a family of proteins that link the plasma membrane to the actin cytoskeleton. The surface expression of moesin on T cells and its role in cell adhesion has not been fully elucidated. Recently, we found that IL-2 peptides generated by elastase modified the adhesion of activated T cells to ECM ligands. Here, we further examined the adhesion regulatory effects of EFLNRWIT, one of the IL-2 peptides, as well as the existence and putative function of its receptor on T cells. We found that when presented to T cells in the absence of another activator, the EFLNRWIT peptide induced cell adhesion to vessel wall and ECM components. Binding of a radiolabeled peptide to T cells, precipitation with the immobilized peptide, and amino acid sequencing of the precipitated protein revealed that EFLNRWIT exerts its function via a cell surface-expressed moesin-like moiety, whose constitutive expression on T cells was increased after activation. This notion was further supported by our findings that: 1) anti-moesin mAb inhibited the binding of T cells to the immobilized EFLNRWIT peptide, 2) immobilized recombinant moesin bound the IL-2 peptide, and 3) soluble moesin inhibited the EFLNRWIT-induced T cell adhesion to fibronectin. Interestingly, moesin appears to be generally involved in T cell responses to adhesion-regulating signals. Thus, the IL-2 peptide EFLNRWIT appears to exert its modulating capacities via an adhesion-regulating moesin-like receptor.

Anti-Moesin Antibodies in the Serum of Patients with Aplastic Anemia Stimulate Peripheral Blood Mononuclear Cells to Secrete TNF-α and IFN-γ

“…This membranelinking protein is expressed by various blood cells including megakaryocytes and granulocytes (23), but its expression was thought to be localized inside the cell membrane and not on the cell surface. Some studies revealed that anti-moesin Abs could bind to the surface of T cells (18) and macrophages (19) in keeping with our observation. However, none of the previous studies characterized the cell surface protein recognized by the anti-moesin Abs.…”

“…Moesin is an intracellular protein that links the cell membrane and cytoskeleton, and mediates the formation of microtubules and cell adhesion sites as well as ruffling of the cell membrane (17). On the other hand, some reports have identified molecules that were recognized by anti-moesin mAbs on the surface of blood cells such as T cells and macrophages (18,19). Because these immune cells are an important source of myelosuppressive cytokines such as TNF-␣ and IFN-␥, it is conceivable that anti-moesin Abs in AA patients may bind such moesin-like molecules on these immune cells and affect the cytokine secretion from these cells.…”

Cell surface-expressed moesin-like HDL/apoA-I binding protein promotes cholesterol efflux from human macrophages

“…Although moesin has a cell surface domain involved in the binding of lipopolysaccharides (21), IL-2 fragments (22), and human immunodeficiency virus type 1 envelope protein gp 120 (23), moesin has no signal peptide, is not expressed on the cell surface, and is not a GPI-anchored type protein. In this study, we demonstrated that the newly purified apoA-I/HDL binding protein is expressed on the cell surface, exclusively on macrophages, and is a GPIanchored type.…”

Role for Moesin in Lipopolysaccharide-Stimulated Signal Transduction

“…In areas of inflammation, Masumoto et al (26) has shown moesin to be expressed in both the center and periphery of neutrophils. Moesin has been reported to have diverse biological functional activities, ranging from a structural protein to a receptor (5,16,37,40,47,51).…”