TY - JOUR
T1 - Signal transduction by HLA class II molecules in human T cells
T2 - Induction of LFA-1-dependent and independent adhesion
AU - Ødum, Niels
AU - Yoshizumi, Hideyuki
AU - Okamoto, Yasuhiro
AU - Kamikawaji, Nobuhiro
AU - Kimura, Akinori
AU - Nishimura, Yasuharu
AU - Sasazuki, Takehiko
N1 - Funding Information:
The authors thaJenfkf reyA . Ledbetter, NitDina mlea, nd SusanR adka (Bristol Meyers-Squibb, SePaatutlleM )a; rtin, Dan Geragthayn, dS teveR osenma(nF redH utchinsoCn an-cer Research Center, SeattlAe.) ;A Dizra. wa(H okkaido University) and Steven J. Bun(aDkaonffa -FabCera ncer Institute, Bostonf)o r their generous goifft asn tibodieasn; d DrY. oshi-masa Uehara (National Insotift uHteea lth, Tokyofo) r the generous goifft herbimyciAn. The authors gratefully thank Anne-Mette Borre Carfloserm n aking the figuarnedsp repar-ing the manuscript. This wwaosrs ku pported in part by the DanishM edicalA ssociation (Ligeforeningens Forsknings-fond), Hoffbundmager Aage FBoanndgK,s ong Christian den X's Fond, Danmark-Amerika Fo(nDdaent ish-American Foundation), abnyda grant-in-aid (63440028) and supported by the Ministroyf Education, Scienacned,C ulture, Japan.
PY - 1992/10
Y1 - 1992/10
N2 - 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.
AB - 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.
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U2 - 10.1016/0198-8859(92)90014-E
DO - 10.1016/0198-8859(92)90014-E
M3 - Article
C2 - 1286978
AN - SCOPUS:0027074871
VL - 35
SP - 71
EP - 84
JO - Human Immunology
JF - Human Immunology
SN - 0198-8859
IS - 2
ER -