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Degradation of T Cell Receptor (TCR)–CD3- Complexes after Antigenic Stimulation

From the Basel Institute for Immunology, CH-4005, Basel, Switzerland

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- 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-, and 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- 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 chain degradation, leading to the accumulation of 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.

The Basel Institute for Immunology was founded and is supported by Hoffman-La Roche Ltd. Co., Basel, Switzerland.

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