Degradation of T cell receptor (TCR)-CD3-zeta complexes after antigenic stimulation.
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.
Valitutti
S
S
Basel Institute for Immunology, CH-4005, Basel, Switzerland.
Müller
S
S
Salio
M
M
Lanzavecchia
A
A
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation; D008247:Lysosomes / Q000187:drug effects / Q000502:physiology; D018942:Macrolides; D010446:Peptide Fragments / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013744:Tetanus Toxin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000941:Antigens; D004791:Enzyme Inhibitors; D018942:Macrolides; D010446:Peptide Fragments; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D013744:Tetanus Toxin; C036978:concanamycin A; D007371:Interferon-gamma; C040929:bafilomycin A1; D006180:Proton-Translocating ATPases; D002118:Calcium