Opposing effects of protein tyrosine kinase inhibitors on the monoclonal antibody induced internalization of CD3 and CD4 antigens.
We have previously demonstrated that the monoclonal antibody (mAb)-induced modulation of CD3 and CD4 antigens from the surface of human peripheral blood lymphocytes is not dependent from protein kinase C activity (Thuillier et al., Eur. J. Immunol. 1990. 20:1197). In the present report we study the effect of genistein and of herbimycin A, two potent inhibitors of protein tyrosine kinases (PTK), on the mAb-induced modulation of CD3 and CD4 surface antigens. Both genistein and herbimycin inhibited the mAb-induced internalization of CD3 and, in contrast, facilitated that of CD4 antigen. These results indicate that the mAb-induced modulation of CD3 is essentially dependent on the PTK pathway, whereas PTK appear to negatively regulate the mAb-induced modulation of CD4.
Thuillier
L
L
INSERM U 132, Hôpital Necker-Enfants Malades, Paris, France.
Pérignon
J L
JL
Selz
F
F
Griscelli
C
C
Fischer
A
A
D000911:Antibodies, Monoclonal; D016525:Antigenic Modulation; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D016227:Benzoquinones; D017252:CD3 Complex; D015704:CD4 Antigens / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000502:physiology*; D019833:Genistein; D006801:Humans; D066298:In Vitro Techniques; D007529:Isoflavones / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D011809:Quinones / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D017828:Rifabutin / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D016227:Benzoquinones; D017252:CD3 Complex; D015704:CD4 Antigens; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D011809:Quinones; D011948:Receptors, Antigen, T-Cell; D010566:Virulence Factors, Bordetella; D017828:Rifabutin; C020754:herbimycin; D002772:Cholera Toxin; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins