ArticleThe Journal of experimental medicine2005
Coexistence of multivalent and monovalent TCRs explains high sensitivity and wide range of response.
Article in The Journal of experimental medicine, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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147 citing papers in PubMed.
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- Coupling Molecular and Cellular Dynamics in a Large-Scale Monte Carlo Simulation.International journal of molecular sciences · 2025Article
- From TCR fundamental research to innovative chimeric antigen receptor design.Nature reviews. Immunology · 2025Review
- DNA origami: Interrogating the nano-landscape of immune receptor activation.Biophysical journal · 2024Review
- Optimized BCMA/CS1 bispecific TRuC-T cells secreting IL-7 and CCL21 robustly control multiple myeloma.Frontiers in immunology · 2024Article
- Nanoscale CAR Organization at the Immune Synapse Correlates with CAR-T Effector Functions.Cells · 2023Article
- Decoding the crosstalk between mevalonate metabolism and T cell function.Immunological reviews · 2023Review
- Hyperstabilization of T cell microvilli contacts by chimeric antigen receptors.The Journal of cell biology · 2023Article
- T Cell Microvilli: Finger-Shaped External Structures Linked to the Fate of T Cells.Immune network · 2023Review
- Opto-APC: Engineering of cells that display phytochrome B on their surface for optogenetic studies of cell-cell interactions.Frontiers in molecular biosciences · 2023Article
- Discovering immunoreceptor coupling and organization motifs.Frontiers in immunology · 2023Article
- Pre-organized landscape of T cell surface.Frontiers in immunology · 2023Review
- Tetraspanin-5-mediated MHC class I clustering is required for optimal CD8 T cell activation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
87 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
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Abstract
A long-standing paradox in the study of T cell antigen recognition is that of the high specificity-low affinity T cell receptor (TCR)-major histocompatibility complex peptide (MHCp) interaction. The existence of multivalent TCRs could resolve this paradox because they can simultaneously improve the avidity observed for monovalent interactions and allow for cooperative effects. We have studied the stoichiometry of the TCR by Blue Native-polyacrylamide gel electrophoresis and found that the TCR exists as a mixture of monovalent (alphabetagammaepsilondeltaepsilonzetazeta) and multivalent complexes with two or more ligand-binding TCRalpha/beta subunits. The coexistence of monovalent and multivalent complexes was confirmed by electron microscopy after label fracture of intact T cells, thus ruling out any possible artifact caused by detergent solubilization. We found that although only the multivalent complexes become phosphorylated at low antigen doses, both multivalent and monovalent TCRs are phosphorylated at higher doses. Thus, the multivalent TCRs could be responsible for sensing low concentrations of antigen, whereas the monovalent TCRs could be responsible for dose-response effects at high concentrations, conditions in which the multivalent TCRs are saturated. Thus, besides resolving TCR stoichiometry, these data can explain how T cells respond to a wide range of MHCp concentrations while maintaining high sensitivity.
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