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A lysosomal protein negatively regulates surface T cell antigen receptor expression by promoting CD3zeta-chain degradation.
- Source :
-
Immunity [Immunity] 2008 Jul 18; Vol. 29 (1), pp. 33-43. - Publication Year :
- 2008
-
Abstract
- Modulation of surface T cell antigen receptor (TCR) expression is an important mechanism for the regulation of immune responses and the prevention of T cell hyperactivation and autoimmunity. The TCR is rapidly internalized after antigen stimulation and then degraded in lysosomes. However, few of the molecules involved in this process have been identified. We demonstrate that the lysosomal protein LAPTM5 negatively regulated surface TCR expression by specifically interacting with the invariant signal-transducing CD3zeta chain and promoting its degradation without affecting other CD3 proteins, CD3epsilon, CD3delta, or CD3gamma. TCR downmodulation required the polyproline-tyrosine motifs and the ubiquitin-interacting motif of LAPTM5. LAPTM5 deficiency resulted in elevated TCR expression on both CD4(+)CD8(+) thymocytes and spleen T cells after CD3 stimulation, as well as enhanced T cell responses in vitro and in vivo. These results identify a lysosomal protein important for CD3zeta degradation and illustrate a unique mechanism for the control of surface TCR expression and T cell activation.
- Subjects :
- Animals
Flow Cytometry
Fluorescent Antibody Technique
Immediate-Early Proteins immunology
Immunoblotting
Immunoprecipitation
Membrane Proteins immunology
Mice
Mice, Knockout
Proteins immunology
Proteins metabolism
Receptors, Antigen, T-Cell immunology
T-Lymphocytes immunology
CD3 Complex metabolism
Immediate-Early Proteins metabolism
Lymphocyte Activation immunology
Membrane Proteins metabolism
Receptors, Antigen, T-Cell metabolism
T-Lymphocytes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4180
- Volume :
- 29
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 18619870
- Full Text :
- https://doi.org/10.1016/j.immuni.2008.04.024