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CD8 expression allows T cell signaling by monomeric peptide-MHC complexes
J Delon1, C Grégoire, B Malissen
1Laboratoire d'Immunologie Cellulaire UMR CNRS 7627 CERVI, Paris, France.
Immunity
|November 7, 1998
Summary
Soluble peptide-MHC monomers can trigger T-cell receptor (TCR) signaling in CD8+ T cells. This requires intact CD8 coreceptor function, suggesting a new model for antigen recognition during T cell activation.
Area of Science:
- Immunology
- Cellular Signaling
- T Cell Biology
Background:
- T-cell receptor (TCR) signaling is crucial for adaptive immunity.
- The conventional model of TCR-CD3 complex cross-linking may not fully explain signaling at low antigen densities.
- Antigen-presenting cells often display limited numbers of specific peptide-MHC complexes.
Purpose of the Study:
- To investigate an alternative model for T cell antigen recognition.
- To determine the role of monomeric peptide-MHC interactions in TCR signaling.
- To elucidate the necessity of the CD8 coreceptor in this process.
Main Methods:
- Utilized soluble peptide-MHC monomers to stimulate T cells.
- Measured calcium (Ca2+) responses as an indicator of T cell activation.
- Disrupted CD8:MHC and CD8:Lck interactions to assess their impact.
Main Results:
- Monomeric soluble peptide-MHC successfully triggered Ca2+ responses in CD8alphabeta+ T cells.
- No Ca2+ response was observed in CD8- T cells.
- Preventing CD8:MHC or CD8:Lck interactions abolished the signaling response.
Conclusions:
- An intact CD8 coreceptor is essential for effective TCR signaling induced by monomeric peptide-MHC.
- This interaction suggests a heterodimerization model of TCR and CD8 engagement by peptide-MHC.
- This mechanism may represent the physiological pathway for antigen-specific T cell signal transduction.