Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion.
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.
Odum
N
N
Department of Genetics, Kyushu University, Fukuoka, Japan.
Yoshizumi
H
H
Okamoto
Y
Y
Kamikawaji
N
N
Kimura
A
A
Nishimura
Y
Y
Sasazuki
T
T
D000470:Alkaloids / Q000494:pharmacology; D015703:Antigens, CD / Q000502:physiology; D016590:Aphidicolin / Q000494:pharmacology; D016227:Benzoquinones; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology*; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology; D003080:Cold Temperature / Q000009:adverse effects; D003571:Cytochalasin B / Q000494:pharmacology; D003572:Cytochalasins / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000502:physiology*; D006801:Humans; D047029:Lactams, Macrocyclic; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D016685:Mitomycin / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000276:immunology*; D019311:Staurosporine; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D015703:Antigens, CD; D016227:Benzoquinones; D003572:Cytochalasins; D006684:HLA-DR Antigens; D047029:Lactams, Macrocyclic; D016169:Lymphocyte Function-Associated Antigen-1; D011809:Quinones; D017828:Rifabutin; C007215:cytochalasin E; D016590:Aphidicolin; D003571:Cytochalasin B; D016048:Dideoxyadenosine; D016685:Mitomycin; C020754:herbimycin; C021008:2',5'-dideoxyadenosine; D004492:Edetic Acid; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate; D003078:Colchicine