Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion
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Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells was recently reported to induce homotypic aggregation through activation of protein kinase C (PKC) and mediated by CD11a/CD54 (LFA-1/CAM-1) adhesion molecules. Here, we report that moAbs directed against framework DR, but neither DR1, 2- and DRw52- nor DQ- and DP-specific moABs induced homotypic aggregation of antigen- and alloantigen-activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation was essentially unaffected. A potent inhibitor of PKC, staurosporin, inhibited both moAb- and PMA-induced aggregation responses. The aggregation responses were completely inhibited by low temperatures, cytochalasins B and E, and partly inhibited by EDTA and CD18 moAbs, but unaffected by aphidicolin, mitomycin C, an adenylate cyclase inhibitor (2'5'-dideoxyadenosine), and moAbs against other adhesion molecules (CD2/CD58 [LFA-3], CD28/CD28 ligand B7, CD4, and CD44). In conclusion, HLA class-II-induced aggregation responses in activated T cells appear to involve PTK and PKC activation and to be mediated through CD11a-dependent and independent adhesion pathways.
Original language | English |
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Journal | Human Immunology |
Volume | 35 |
Issue number | 2 |
Pages (from-to) | 71-84 |
Number of pages | 13 |
ISSN | 0198-8859 |
Publication status | Published - 1992 |
Bibliographical note
Keywords: Alkaloids; Antigens, CD; Aphidicolin; Benzoquinones; Cell Adhesion; Cell Line; Colchicine; Cold Temperature; Cytochalasin B; Cytochalasins; Dideoxyadenosine; Dose-Response Relationship, Drug; Edetic Acid; HLA-DR Antigens; Humans; Lactams, Macrocyclic; Lymphocyte Function-Associated Antigen-1; Mitomycin; Protein Kinase C; Protein-Tyrosine Kinases; Quinones; Signal Transduction; Staurosporine; T-Lymphocytes; Tetradecanoylphorbol Acetate
ID: 10636185