Masking of the CD3 gamma di-leucine-based motif by zeta is required for efficient T-cell receptor expression

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 -