Expression of ICAM-3 on human epidermal dendritic cells

Three counter-receptors for LFA-1 of the immunoglobulin family have been discovered: ICAM-1, ICAM-2, and ICAM-3. Despite their homologies, their patterns of expression suggest specialized roles. The finding that ICAM-3 is much better expressed than other LFA-1 ligands on monocytes and resting T cells, and that this discovery may be important in the initiation of immune responses prompted us to search for the expression of ICAM-3 by human epidermal Langerhans cells (LC). Six out of eight different ICAM-3 monoclonal antibodies were found to be reactive with epidermal LC. Immunoelectron-microscopy staining revealed that 100% of freshly-isolated, typical Birbeck granules containing LC expressed ICAM-3. After one day and three days of culture, 100% of LC still expressed ICAM-3, but the staining intensity was decreased by 58% and 76% respectively. Immunoprecipitation of 125I surface-labeled LC with anti-ICAM-3 antibodies revealed a polypeptide with apparent M(r) of 122,000-125,000. To determine whether ICAM-3 was involved in LC function, mixed epidermal cell-lymphocyte reactions were performed with freshly isolated LC in the presence of various concentrations of different anti-ICAM-3 antibodies. Among the different antibodies tested, HP2/19 and CBR-IC3/1 were found to partially block the reaction in a dose-dependent manner, suggesting that ICAM-3 represents a new molecule involved in the initiation of the immune response driven by epidermal LC.