Degradation of T cell receptor (TCR)–CD3-ζ complexes after antigenic stimulation

S Valitutti, S Müller, M Salio… - The Journal of …, 1997 - rupress.org
S Valitutti, S Müller, M Salio, A Lanzavecchia
The Journal of experimental medicine, 1997rupress.org
T cell activation by specific antigen results in a rapid and long-lasting downregulation of
triggered T cell receptors (TCRs). In this work, we investigated the fate of downregulated
TCR–CD3-ζ complexes. T cells stimulated by peptide-pulsed antigen-presenting cells
(APCs) undergo an antigen dose-dependent decrease of the total cellular content of TCR-β,
CD3-ε, and ζ chains, as detected by FACS® analysis on fixed and permeabilized T–APC
conjugates and by Western blot analysis on cell lysates. The time course of CD3-ζ chain …
T cell activation by specific antigen results in a rapid and long-lasting downregulation of triggered T cell receptors (TCRs). In this work, we investigated the fate of downregulated TCR– CD3-ζ complexes. T cells stimulated by peptide-pulsed antigen-presenting cells (APCs) undergo an antigen dose-dependent decrease of the total cellular content of TCR-β, CD3-ε, and ζ chains, as detected by FACS® analysis on fixed and permeabilized T–APC conjugates and by Western blot analysis on cell lysates. The time course of CD3-ζ chain consumption overlaps with that of TCR downregulation, indicating that internalized TCR–CD3 complexes are promptly degraded. Inhibitors of lysosomal function (bafilomycin A1, folimycin) markedly reduced ζ chain degradation, leading to the accumulation of ζ chain in large Lamp1+ vesicles. These results indicate that in T cell–APC conjugates, triggered TCRs are rapidly removed from the cell surface and are degraded in the lysosomal compartment.
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