Masking of the CD3 gamma di-leucine-based motif by zeta is required for efficient T-cell receptor expression.
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.
Lauritsen
Jens Peter H
JP
Institute of Medical Microbiology and Immunology, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
Bonefeld
Charlotte Menné
CM
von Essen
Marina
M
Nielsen
Martin Weiss
MW
Rasmussen
Anette Bødker
AB
Ødum
Niels
N
Dietrich
Jes
J
Geisler
Carsten
C
D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis / Q000235:genetics / Q000276:immunology / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; D011948:Receptors, Antigen, T-Cell