DEGRADATION OF T-CELL RECEPTOR (TCR)-CD3-XI COMPLEXES AFTER ANTIGENIC-STIMULATION

T cell activation by specific antigen results in a rapid and long-last ing downregulation of triggered T cell receptors (TCRs). In this work, we investigated the fate of downregulated TCR-CD3-zeta complexes. T c ells stimulated by peptide-pulsed antigen-presenting cells (APCs) unde rgo an antigen dose-dependent decrease of the total cellular content o f TCR-beta, CD3-epsilon, and zeta chains, as detected by FACS(R) analy sis on fixed and permeabilized T-APC conjugates and by Western blot an alysis 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 func tion (bafilomycin A1, folimycin) markedly reduced zeta chain degradati on, leading to the accumulation of zeta chain in large Lamp1(+) vesicl es. These results indicate that in T cell-APC conjugates, triggered TC Rs are rapidly removed from the cell surface and are degraded in the l ysosomal compartment.