The human neural cell adhesion molecule L1 functions as a costimulatory molecule in T cell activation.
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.
Balaian
L B
LB
Stem Cell Laboratory, University of California San Diego, La Jolla, USA.
Moehler
T
T
Montgomery
A M
AM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D039841:Leukocyte L1 Antigen Complex; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D010835:Phytohemagglutinins