Molecular mechanisms involved in T cell receptor triggering
Kaushik Choudhuri1, P Anton van der Merwe
1Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom.
Seminars in Immunology
|June 15, 2007
Summary
Understanding T cell receptor (TCR) triggering remains a challenge. Current evidence suggests TCR triggering involves a combination of segregation and conformational changes, with aggregation amplifying the signal.
Area of Science:
- Immunology
- Cellular Signaling
- Molecular Biology
Background:
- The precise mechanism of T cell receptor (TCR) signal transduction across the plasma membrane, known as TCR triggering, is not fully understood.
- Proposed mechanisms include TCR aggregation, conformational changes, or segregation upon pMHC ligand binding.
Purpose of the Study:
- To elucidate the fundamental mechanisms underlying TCR triggering.
- To evaluate the roles of aggregation, conformational change, and segregation in initiating and amplifying TCR signals.
Main Methods:
- Review and synthesis of existing structural and biochemical studies on TCR-pMHC interactions.
- Analysis of evidence supporting or refuting proposed TCR triggering models.
Main Results:
- TCR aggregation is unlikely to initiate triggering due to low pMHC ligand density but likely enhances downstream signaling.
- Structural studies have not definitively confirmed or excluded a conformational change mechanism but have ruled out specific types.
- Size-induced segregation of the bound TCR from inhibitory phosphatases appears necessary but insufficient as the sole mechanism.
Conclusions:
- TCR triggering likely results from a synergistic interplay between segregation and conformational changes.
- Subsequent aggregation of TCRs contributes to signal amplification.
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