Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity.
At the interface between T cell and antigen-presenting cell (APC), peptide antigen presented by MHC (pMHC) binds to the T cell receptor (TCR) and initiates signaling. The mechanism of TCR signal initiation, or triggering, remains unclear. An interesting aspect of this puzzle is that although soluble...
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| Language: | English |
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Public Library of Science (PLoS)
2008-02-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0060043&type=printable |
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| author | Zhengyu Ma Kim A Sharp Paul A Janmey Terri H Finkel |
| author_facet | Zhengyu Ma Kim A Sharp Paul A Janmey Terri H Finkel |
| author_sort | Zhengyu Ma |
| collection | DOAJ |
| description | At the interface between T cell and antigen-presenting cell (APC), peptide antigen presented by MHC (pMHC) binds to the T cell receptor (TCR) and initiates signaling. The mechanism of TCR signal initiation, or triggering, remains unclear. An interesting aspect of this puzzle is that although soluble agonist pMHCs cannot trigger TCR even at high concentrations, the same ligands trigger TCR very efficiently on the surface of APCs. Here, using lipid bilayers or plastic-based artificial APCs with defined components, we identify the critical APC-associated factors that confer agonist pMHCs with such potency. We found that CD4+ T cells are triggered by very low numbers of monomeric agonist pMHCs anchored on fluid lipid bilayers or fixed plastic surfaces, in the absence of any other APC surface molecules. Importantly, on bilayers, plastic surfaces, or real APCs, endogenous pMHCs did not enhance TCR triggering. TCR triggering, however, critically depended upon the adhesiveness of the surface and an intact T cell actin cytoskeleton. Based on these observations, we propose the receptor deformation model of TCR triggering to explain the remarkable sensitivity and specificity of TCR triggering. |
| format | Article |
| id | doaj-art-fef7c72be6d34792a6cd7c0956fcfbdb |
| institution | OA Journals |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2008-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-fef7c72be6d34792a6cd7c0956fcfbdb2025-08-20T02:02:44ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852008-02-0162e4310.1371/journal.pbio.0060043Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity.Zhengyu MaKim A SharpPaul A JanmeyTerri H FinkelAt the interface between T cell and antigen-presenting cell (APC), peptide antigen presented by MHC (pMHC) binds to the T cell receptor (TCR) and initiates signaling. The mechanism of TCR signal initiation, or triggering, remains unclear. An interesting aspect of this puzzle is that although soluble agonist pMHCs cannot trigger TCR even at high concentrations, the same ligands trigger TCR very efficiently on the surface of APCs. Here, using lipid bilayers or plastic-based artificial APCs with defined components, we identify the critical APC-associated factors that confer agonist pMHCs with such potency. We found that CD4+ T cells are triggered by very low numbers of monomeric agonist pMHCs anchored on fluid lipid bilayers or fixed plastic surfaces, in the absence of any other APC surface molecules. Importantly, on bilayers, plastic surfaces, or real APCs, endogenous pMHCs did not enhance TCR triggering. TCR triggering, however, critically depended upon the adhesiveness of the surface and an intact T cell actin cytoskeleton. Based on these observations, we propose the receptor deformation model of TCR triggering to explain the remarkable sensitivity and specificity of TCR triggering.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0060043&type=printable |
| spellingShingle | Zhengyu Ma Kim A Sharp Paul A Janmey Terri H Finkel Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity. PLoS Biology |
| title | Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity. |
| title_full | Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity. |
| title_fullStr | Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity. |
| title_full_unstemmed | Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity. |
| title_short | Surface-anchored monomeric agonist pMHCs alone trigger TCR with high sensitivity. |
| title_sort | surface anchored monomeric agonist pmhcs alone trigger tcr with high sensitivity |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.0060043&type=printable |
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