Expression Dynamics of the O-Glycosylated Proteins Recognized by Amaranthus leucocarpus Lectin in T Lymphocytes and Its Relationship With Moesin as an Alternative Mechanism of Cell Activation.

T lymphocyte activation begins with antigen/MHC recognition by the TCR/CD3 complex followed by a costimulatory signal provided by CD28. The search for novel costimulatory molecules has been extensive due to their potential use as immunotherapeutic targets. Although some molecules have been identified, they are unable to provide sustainable signaling to allow for proper T cell activation and proliferation. It has been shown that the Amaranthus leucocarpus lectin (ALL) can be used as an in vitro costimulator of CD4+ lymphocytes in the presence of anti-CD3 mAb; this lectin specifically recognizes O-glycans of the Galß1-3GalNAc-O-Ser/Thr type, including a 70-kDa moesin-like protein that has been suggested as the costimulatory molecule. However, the identity of this molecule has not been confirmed and such costimulation has not been analyzed in CD8+ lymphocytes. We show herein that the expression kinetics of the glycoproteins recognized by ALL (gpALL) is different in CD4+ and CD8+ T cells, unlike moesin expression. Results from IP experiments demonstrate that the previously described 70-kDa moesin-like protein is an O-glycosylated form of moesin (O-moesin) and that in vitro stimulation with anti-CD3 and anti-moesin mAb induces expression of the activation molecules CD69 and CD25, proliferation and IL-2 production as efficiently as cells costimulated with ALL or anti-CD28. Overall, our results demonstrate that O-moesin is expressed in CD4+ and CD8+ T lymphocytes and that moesin provides a new costimulatory activation signal in both T cell subsets.

Relevance of glycans in the interaction between T lymphocyte and the antigen presenting cell.

The immunological synapse promotes receptors and ligands interaction in the contact interface between the T lymphocyte and the antigen presenting cell; glycosylation of the proteins involved in this biological process favors regulation of molecular interactions and development of the T lymphocyte effector response. Glycans in the immunological synapse influence cellular and molecular processes such as folding, expression, and structural stability of proteins, they also mediate ligand-receptor interaction and propagation of the intracellular signaling or inhibition of uncontrolled cellular activation that could lead to the development of autoimmunity, among others. It has been suggested that altered glycosylation of proteins that participate in the immunological synapse affects the signaling processes and cell proliferation, as well as exacerbation of the effector mechanisms of T cells that trigger systemic damage and autoimmunity. Understanding the role of glycans in the immune response has allowed for advances in the development of immunotherapies in different fields through the controlled and specific activation of the immune response. This review describes the structural and biological aspects of glycans associated with some molecules present in the immunological synapse, providing information that allows understanding the function of glycosylation in the interaction between the T lymphocyte and the antigen-presenting cell, as well as its impact on signaling and development regulation of T lymphocytes effector response.