TY - JOUR
T1 - Masking of the CD3 gamma di-leucine-based motif by zeta is required for efficient T-cell receptor expression
AU - Lauritsen, Jens Peter H
AU - Bonefeld, Charlotte Menné
AU - von Essen, Marina
AU - Nielsen, Martin Weiss
AU - Rasmussen, Anette Bødker
AU - Ødum, Niels
AU - Dietrich, Jes
AU - Geisler, Carsten
N1 - Keywords: Amino Acid Motifs; Amino Acid Sequence; Animals; Antigens, CD3; Cell Line; Endocytosis; Gene Expression Regulation; Humans; Molecular Sequence Data; Receptors, Antigen, T-Cell
PY - 2004
Y1 - 2004
N2 - The T-cell receptor (TCR) is a multimeric receptor composed of the Ti alpha beta heterodimer and the noncovalently associated CD3 gamma delta epsilon and zeta(2) chains. All of the TCR chains are required for efficient cell surface expression of the TCR. Previous studies on chimeric molecules containing the di-leucine-based endocytosis motif of the TCR subunit CD3 gamma have indicated that the zeta chain can mask this motif. In this study, we show that successive truncations of the cytoplasmic tail of zeta led to reduced surface expression levels of completely assembled TCR complexes. The reduced TCR expression levels were caused by an increase in the TCR endocytic rate constant in combination with an unaffected exocytic rate constant. Furthermore, the TCR degradation rate constant was increased in cells with truncated zeta. Introduction of a CD3 gamma chain with a disrupted di-leucine-based endocytosis motif partially restored TCR expression in cells with truncated zeta chains, indicating that the zeta chain masks the endocytosis motif in CD3 gamma and thereby stabilizes TCR cell surface expression.
AB - The T-cell receptor (TCR) is a multimeric receptor composed of the Ti alpha beta heterodimer and the noncovalently associated CD3 gamma delta epsilon and zeta(2) chains. All of the TCR chains are required for efficient cell surface expression of the TCR. Previous studies on chimeric molecules containing the di-leucine-based endocytosis motif of the TCR subunit CD3 gamma have indicated that the zeta chain can mask this motif. In this study, we show that successive truncations of the cytoplasmic tail of zeta led to reduced surface expression levels of completely assembled TCR complexes. The reduced TCR expression levels were caused by an increase in the TCR endocytic rate constant in combination with an unaffected exocytic rate constant. Furthermore, the TCR degradation rate constant was increased in cells with truncated zeta. Introduction of a CD3 gamma chain with a disrupted di-leucine-based endocytosis motif partially restored TCR expression in cells with truncated zeta chains, indicating that the zeta chain masks the endocytosis motif in CD3 gamma and thereby stabilizes TCR cell surface expression.
U2 - 10.1111/j.1600-0854.2004.00211.x
DO - 10.1111/j.1600-0854.2004.00211.x
M3 - Journal article
C2 - 15296492
SN - 1398-9219
VL - 5
SP - 672
EP - 684
JO - Traffic
JF - Traffic
IS - 9
ER -