LFA-1-and ICAM-1-dependent homotypic aggregation of human thymocytes induced by JL1 engagement

Cell-cell adhesion is essential for the appropriate immune response, differ entiation, and migration of lymphocytes. This important physiological event is reflected in vitro by homotypic cell aggregation. We have previously re ported that, a 120 kDa cell surface glycoprotein, JL1, is a unique protein specifically expressed by immature double positive (DP) human thymocytes wh ich are in the process of positive and negative selections through the inte raction between thymocyte and antigen-presenting cells (APCs), The function of the JL1 molecule, however, is yet to be identified, We show here that a nti-JL1 monoclonal antibody (mAb) induced the homotypic aggregation of huma n thymocytes in a temperature- and Mg2+-dependent manner. It required an in tact cytoskeleton and the interaction between leucocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) since it was blocked by cytochalasin B and D, and mAb against LFA-1 and ICAM-1 which are known to be involved in the aggregation of thymocytes. Translocation o f phosphatidylserine (PtdSer) through the cell membrane was not detected, i mplying that the molecular mechanism of JL-1-induced homotypic aggregation is different from that of CD99-induced homotypic aggregation. In summary, J L1 is a cell surface molecule that induces homotypic adhesion mediated by t he LFA-1 and ICAM-1 interaction and cytoskeletal reorganization, These find ings suggest that JL1 may be an important regulator of thymocyte developmen t and thymocyte-APC interaction.