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 norma l neurological development. Despite being described as a neural CAM, we hav e documented L1 expression by antigen-presenting cells of myelomonocytic or igin. Here we demonstrate that L1 can function as a costimulatory molecule in T cell activation. A monoclonal antibody that abrogates L1-L1 hemophilic binding significantly reduced mixed leukocyte responses initialed by allog eneic L1(+) dendritic cells. Autologous T cell activation in response to ph ytohemagglutinin was also inhibited by blockade of L1. In accordance with t hese results. transfection of human L1 into a murine myeloma cell line sign ificantly increased the capacity of these cells to stimulate xenogeneic T c ell 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.