Function of adhesion molecules lymphocyte function-associated antigen-3 and intercellular adhesion molecule-1 on human epidermal Langerhans cells 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 between adhesion molecules on the APC and their ligands on T cells. We determined the presence of adhesion molecules on human epidermal Langerhans cells (LC) and their role in Ag-specific T cell activation. Freshly isolated LC did not display ICAM-1 (CD54), ICAM-2, LFA-1 (CD11a), and LFA-3 (CD58), as detected by double-color FACS analysis, using HLA-DR expression for LC identification. Upon culture, LC clearly expressed ICAM-1 and LFA-3, both already detectable after 1 day, reaching a plateau at day 2. ICAM-2 and LFA-1 were undetectable on cultured LC and attempts to induce this expression by different culture conditions remained unsuccessful. mAb against ICAM-1, LFA-1, LFA-3, and CD2, continuously present during culture, inhibited the T cell proliferative response to Candida albicans presented by cultured LC. Pretreatment of LC and/or 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 cell 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 initiation 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 cell response. The high expression of these accessory molecules enable LC, at least in part, to perform their powerful Ag-presenting function.
Teunissen
M B
MB
Department of Dermatology, University of Amsterdam, The Netherlands.
Rongen
H A
HA
Bos
J D
JD
D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism*; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D004817:Epidermis / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007801:Langerhans Cells / Q000276:immunology*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D018799:Intercellular Adhesion Molecule-1