Effect of hypertonicity and monensin on CD3/TCR surface expression in human T cells.
Pretreatment of T lymphocytes with anti-CD3 or anti-TCR mAb results in the disappearance of the T cell receptor complex (TCR/CD3) from the cell surface. The mechanisms of this down-regulation have not been fully elucidated. We demonstrate here that the modulation of the CD3/TCR complex can be completely inhibited by hypertonic medium, a condition known to block receptor-mediated endocytosis. Consequently, the sequestration of the CD3/TCR complex associated to relevant mAb in acid vesicles did not occur under hypertonicity condition. Moreover, monensin, which is known to interfere with receptor recycling, was found to amplify the CD3/TCR modulation induced by specific mAb and decrease the uptake of 125I-labeled anti-CD3/TCR mAb by T cells. We therefore propose that mAb-CD3/TCR complexes are internalized via coated pits by a receptor-mediated endocytosis and then transported to acid compartments. MAb are degraded in lysosomes during this process, whereas CD3/TCR molecules recycle back to cell surface.
Dallanegra
A
A
INSERM U 210, Faculté de Médicine, Nice Cedex, France.
Schaffar
L
L
Breittmayer
J P
JP
Carpentier
J L
JL
Fehlmann
M
M
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D002999:Clone Cells / Q000187:drug effects / Q000276:immunology; D003034:Coated Pits, Cell-Membrane / Q000187:drug effects / Q000276:immunology; D004705:Endocytosis / Q000187:drug effects; D006801:Humans; D008985:Monensin / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000378:metabolism*; D012462:Saline Solution, Hypertonic; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D012462:Saline Solution, Hypertonic; D008985:Monensin