FUNCTION OF ADHESION MOLECULES LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-3 AND INTERCELLULAR-ADHESION MOLECULE-1 ON HUMAN EPIDERMAL LANGERHANSCELLS IN ANTIGEN-SPECIFIC T-CELL ACTIVATION

In addition to the interaction between the TCR and the MHC/Ag complex on the APC, optimal T cell activation also requires interaction betwee n adhesion molecules on the APC and their ligands on T cells. We deter mined the presence of adhesion molecules on human epidermal Langerhans cells (LC) and their role in Ag-specific T cell activation. Freshly i solated LC did not display ICAM-1 (CD54), ICAM-2, LFA-1 (CD11a), and L FA-3 (CD58), as detected by double-color FACS analysis, using HLA-DR e xpression for LC identification. Upon culture, LC clearly expressed IC AM-1 and LFA-3, both already detectable after 1 day, reaching a platea u at day 2. ICAM-2 and LFA-1 were undetectable on cultured LC and atte mpts to induce this expression by different culture conditions remaine d unsuccessful. mAb against ICAM-1, LFA-1, LFA-3, and CD2, continuousl y present during culture, inhibited the T cell proliferative response to Candida albicans presented by cultured LC. Pretreatment of LC and/o r T cells with mAb indicated that anti-ICAM-1 and anti-LFA-3 inhibited at the LC level, whereas anti-LFA-1 and anti-CD2 inhibited at the T c ell level. The mAb-induced inhibition was dose dependent, but a total blockade of the response was never achieved. Time-course observations revealed that ICAM-1 and LFA-3 on LC only functioned during the initia tion phase of T cell activation. Our study demonstrates that both ICAM -1 and LFA-3 on LC considerably contribute to the generation of a T ce ll response. The high expression of these accessory molecules enable L C, at least in part, to perform their powerful Ag-presenting function.