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

J Exp Med. 1997 May 19;185(10):1859-64. doi: 10.1084/jem.185.10.1859.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / pharmacology
  • Antigen-Presenting Cells / immunology
  • Antigens
  • Calcium / metabolism
  • Clone Cells
  • Down-Regulation
  • Enzyme Inhibitors / pharmacology
  • Flow Cytometry
  • Humans
  • Interferon-gamma / biosynthesis
  • Kinetics
  • Lymphocyte Activation*
  • Lysosomes / drug effects
  • Lysosomes / physiology
  • Macrolides*
  • Peptide Fragments / pharmacology
  • Proton-Translocating ATPases / antagonists & inhibitors
  • Receptor-CD3 Complex, Antigen, T-Cell / biosynthesis*
  • Receptor-CD3 Complex, Antigen, T-Cell / immunology
  • T-Lymphocytes / immunology*
  • Tetanus Toxin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Antigens
  • Enzyme Inhibitors
  • Macrolides
  • Peptide Fragments
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Tetanus Toxin
  • concanamycin A
  • Interferon-gamma
  • bafilomycin A1
  • Proton-Translocating ATPases
  • Calcium