Human T cell activation through the activation-inducer molecule/CD69 enhances the activity of transcription factor AP-1.
The induction of the AP-1 transcription factor has been ascribed to the early events leading to T cell differentiation and activation. We have studied the regulation of AP-1 activity in human peripheral blood T lymphocytes stimulated through the activation inducer molecule (AIM)/CD69 activation pathway. Phorbol esters are required to induce AIM/CD69 cell-surface expression as well as for triggering the proliferation of T cells in conjunction with anti-AIM mAb. Mobility shift assays showed that addition of anti-AIM mAb to PMA-treated T lymphocytes markedly enhanced the binding activity of AP-1 to its cognate sequence, the phorbol ester response element. In contrast, anti-AIM mAb did not induce any change in the binding activity of NF-kappa B, a transcription factor whose activity is also regulated by protein kinase C. The increase in AP-1-binding activity was accompanied by the marked stimulation of the transcription of c-fos but not that of c-jun. Blockade of the DNA-binding complexes with an anti-Fos mAb demonstrated a direct participation of c-Fos in the AP-1 complexes induced by anti-AIM mAb. Most of the AP-1 activity could be eliminated when the anti-AIM mAb was added to the culture medium in the presence of cycloheximide, suggesting that de novo protein synthesis is crucial for the induction of AP-1-binding activity. These data provide the evidence that activation of human peripheral blood T cells through the AIM activation pathway regulate the activity of AP-1. Therefore, this pathway appears as a crucial step in the initiation of early T cell activation events.
Tugores
A
A
S. de Inmunología, Hospital de la Princesa, Madrid, Spain.
Alonso
M A
MA
Sánchez-Madrid
F
F
de Landázuri
M O
MO
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D001483:Base Sequence; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D000099192:CD69 Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007376:Interleukin-2; D037181:Lectins, C-Type; D011493:Protein Kinase C; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate; D000099192:CD69 Antigens