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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-zeta complexes. T cells stimulated by peptide-pulsed antigen-presenting cells (APCs) undergo an antigen dose-dependent decrease of the total cellular content of TCR-beta, CD3-epsilon, and zeta chains, as detected by FACS(R) analysis on fixed and permeabilized T-APC conjugates and by Western blot analysis on cell lysates. The time course of CD3-zeta 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 zeta chain degradation, leading to the accumulation of zeta 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.

Original publication




Journal article


J Exp Med

Publication Date





1859 - 1864


Amino Acid Sequence, Anti-Bacterial Agents, Antigen-Presenting Cells, Antigens, Calcium, Clone Cells, Down-Regulation, Enzyme Inhibitors, Flow Cytometry, Humans, Interferon-gamma, Kinetics, Lymphocyte Activation, Lysosomes, Macrolides, Peptide Fragments, Proton-Translocating ATPases, Receptor-CD3 Complex, Antigen, T-Cell, T-Lymphocytes, Tetanus Toxin