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CD3 delta establishes a functional link between the T cell receptor and CD8
Marie-Agnès Doucey1, Laurence Goffin, Dieter Naeher
1Institute for Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
The Journal of Biological Chemistry
|September 7, 2002
Summary
The CD3 delta protein is crucial for T cell activation and selection. It couples the T cell receptor (TCR) complex with CD8, enabling proper T cell signaling and function.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- T cell activation and selection depend on the T cell receptor (TCR) complex.
- CD8 co-receptor plays a critical role in the function of CD8+ T cells.
- The precise role of CD3 delta in coupling TCR.CD3 with CD8 remains unclear.
Purpose of the Study:
- To investigate the role of CD3 delta in the association between the TCR.CD3 complex and CD8.
- To determine if CD3 delta mediates the coupling of TCR.CD3 with raft-associated CD8.
Main Methods:
- Utilized T cell hybridomas and transgenic mice expressing the T1 TCR.
- Employed co-immunoprecipitation assays to detect protein associations.
- Analyzed TCR aggregate formation and intracellular calcium mobilization upon cross-linking.
Main Results:
- CD8 alpha beta associates with the T cell receptor (TCR) complex in thymocytes and hybridomas expressing the T1 TCR.CD3 complex.
- This association was absent in T1 hybridomas lacking CD3 delta or expressing CD8 alpha alpha.
- CD3 delta was selectively co-immunoprecipitated with anti-CD8 antibodies, confirming an avid association between CD8 and CD3 delta.
Conclusions:
- CD3 delta acts as a crucial linker between the TCR.CD3 complex and raft-associated CD8.
- This CD3 delta-mediated coupling is essential for effective activation and positive selection of CD8+ T cells.