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Architectural changes in the TCR:CD3 complex induced by MHC:peptide ligation
Nicole L La Gruta1, Haiyan Liu, Smaroula Dilioglou
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|March 9, 2004
Summary
T cell activation involves TCR:CD3 complex down-modulation. This study reveals increased free CD3 zeta-chain on the cell surface after T cell stimulation, suggesting a mechanism for selective receptor down-regulation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- T cell activation is marked by TCR:CD3 complex down-modulation.
- The CD3 zeta-chain is crucial for TCR:CD3 complex assembly, transport, and surface expression.
- Molecular mechanisms driving TCR:CD3 down-modulation remain largely unknown.
Purpose of the Study:
- To investigate the relationship between CD3 zeta and the TCRalphabetaCD3epsilondeltagamma complex post-ligation.
- To elucidate the molecular events underlying TCR:CD3 complex down-modulation.
Main Methods:
- Studied T cell activation via MHC:peptide complex ligation.
- Analyzed the cell surface expression and association of CD3 zeta with the TCR:CD3 complex.
- Investigated the role of Src family kinases.
Main Results:
- Significant increase in free surface CD3 zeta not associated with the TCR:CD3 complex post-stimulation.
- MHC:peptide ligation exposes the ordinarily buried NH2 terminus of TCR-associated CD3 zeta.
- These events are dependent on Src family protein tyrosine kinases.
Conclusions:
- Increased free CD3 zeta may result from dissociation or direct transport to the cell surface.
- Exposed CD3 zeta terminus suggests a mechanism for differentiating ligated from unligated TCR.
- These findings propose a pathway for selective TCR down-modulation in T cell activation.