Signal transduction by HLA class II molecules in human T cells: Induction of LFA-1-dependent and independent adhesion

Niels Ødum, Hideyuki Yoshizumi, Yasuhiro Okamoto, Nobuhiro Kamikawaji, Akinori Kimura, Yasuharu Nishimura, Takehiko Sasazuki

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Abstract

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 mo Abs 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 languageEnglish
Pages (from-to)71-84
Number of pages14
JournalHuman Immunology
Volume35
Issue number2
DOIs
Publication statusPublished - Oct 1992

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All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Ødum, N., Yoshizumi, H., Okamoto, Y., Kamikawaji, N., Kimura, A., Nishimura, Y., & Sasazuki, T. (1992). Signal transduction by HLA class II molecules in human T cells: Induction of LFA-1-dependent and independent adhesion. Human Immunology, 35(2), 71-84. https://doi.org/10.1016/0198-8859(92)90014-E