Overexpression of CD82 on human T cells enhances LFA-1 / ICAM-1-mediated cell-cell adhesion: functional association between CD82 and LFA-1 in T cell activation.
We previously demonstrated that CD82, expressed on both T cells and antigen-presenting cells (APC), plays an important role as a co-stimulatory molecule especially in the early phase of T cell activation. We also showed that the CD82 expression level is up-regulated on activated T cells and memory T cells. This up-regulation enhances both T cell-T cell and T cell-APC interactions. In this study, we further investigated the mechanism of CD82-mediated cell-cell adhesion. The enhanced adhesion between CD82-overexpressing Jurkat cells was completely blocked by anti-ICAM-1 / LFA-1 monoclonal antibodies. Increased interaction of LFA-1 with ICAM-1 was further confirmed by enhanced adhesion of CD82-overexpressing Jurkat cells to immobilized ICAM-1-Ig. CD82 co-immunoprecipitated with LFA-1 from Jurkat cells and CD82 and LFA-1 colocalized at an adhesion foci. These results suggest that the T cell stimulation via anti-CD3 cross-linking or phorbol myristate acetate treatment up-regulates CD82 expression, leading to the colocalization of CD82 and LFA-1, and results in enhanced interaction between LFA-1 and ICAM-1. In addition, a blocking experiment using monoclonal antibodies suggested that CD82 and LFA-1 molecules on APC are also important for the optimal activation of T cells. This is the first report that describes the enhancement of cell-cell interaction through LFA-1 and ICAM-1 by the overexpression of another cell surface molecule, CD82.
Shibagaki
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Department of Molecular Biotherapy Research Cancer Chemotherapy Center, Cancer, Institute, Tokyo, Japan.
Hanada
K i
Ki
Yamashita
H
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Shimada
S
S
Hamada
H
H
D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D051861:Kangai-1 Protein; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D011518:Proto-Oncogene Proteins; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*
D015703:Antigens, CD; C497688:CD82 protein, human; D051861:Kangai-1 Protein; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D018799:Intercellular Adhesion Molecule-1