The human neural cell adhesion molecule L1 functions as a costimulatory molecule in T cell activation

• Published in: European journal of immunology 2000-03, Vol.30 (3), p.938-943
• Main Authors: Balaian, Larissa B., Moehler, Thomas, Montgomery, Anthony M. P.
• Format: Article
• Language: English
• Subjects: Activation; Animals; Antibodies, Monoclonal - pharmacology; CD3 Complex - immunology; Cell Line; Costimulation; Dendritic Cells - immunology; Humans; In Vitro Techniques; Leukocyte L1 Antigen Complex; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - pharmacology; Neural Cell Adhesion Molecules - genetics; Neural Cell Adhesion Molecules - immunology; Neural Cell Adhesion Molecules - pharmacology; Phytohemagglutinins - pharmacology; T cell; T-Lymphocytes - immunology; Transfection; Tumor Cells, Cultured
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200003)30:3<938::AID-IMMU938>3.0.CO;2-Q

L1 is a neural cell adhesion molecule (CAM) known to be important for normal neurological development. Despite being described as a neural CAM, we have documented L1 expression by antigen‐presenting cells of myelomonocytic origin. Here we demonstrate that L1 can function as a costimulatory molecule in T cell activation. A monoclonal antibody that abrogates L1‐L1 homophilic binding significantly reduced mixed leukocyte responses initiated by allogeneic L1+ dendritic cells. Autologous T cell activation in response to phytohemagglutinin was also inhibited by blockade of L1. In accordance with these results, transfection of human L1 into a murine myeloma cell line significantly increased the capacity of these cells to stimulate xenogeneic T cell responses. As a costimulatory ligand L1 could represent a novel target for immunotherapeutic intervention and may act as an important intermediary in neuroimmunological processes and disease.