An induced rebinding model of antigen discrimination.
T cells have to detect rare high-affinity 'foreign' peptide MHC (pMHC) ligands among abundant low-affinity 'self'-peptide MHC ligands. It remains unclear how this remarkable discrimination is achieved. Kinetic proofreading mechanisms can provide the required specificity but only...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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2014
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| _version_ | 1826262089633628160 |
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| author | Dushek, O Van Der Merwe, P |
| author_facet | Dushek, O Van Der Merwe, P |
| author_sort | Dushek, O |
| collection | OXFORD |
| description | T cells have to detect rare high-affinity 'foreign' peptide MHC (pMHC) ligands among abundant low-affinity 'self'-peptide MHC ligands. It remains unclear how this remarkable discrimination is achieved. Kinetic proofreading mechanisms can provide the required specificity but only at the expense of much reduced sensitivity. A number of recent observations suggest that pMHC engagement of T cell receptors (TCRs) induces changes such as clustering and/or conformational alterations that enhance subsequent rebinding. We show that inclusion of induced rebinding to the same pMHC in kinetic proofreading models enhances the sensitivity of TCR recognition while retaining specificity. Moreover, induced rebinding is able to reproduce the striking, and hitherto unexplained, 2D membrane-binding properties recently reported for the TCR. |
| first_indexed | 2024-03-06T19:30:51Z |
| format | Journal article |
| id | oxford-uuid:1d6c0399-1816-4b04-baa2-d133b5dfe8df |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:30:51Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:1d6c0399-1816-4b04-baa2-d133b5dfe8df2022-03-26T11:10:43ZAn induced rebinding model of antigen discrimination.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1d6c0399-1816-4b04-baa2-d133b5dfe8dfEnglishSymplectic Elements at Oxford2014Dushek, OVan Der Merwe, PT cells have to detect rare high-affinity 'foreign' peptide MHC (pMHC) ligands among abundant low-affinity 'self'-peptide MHC ligands. It remains unclear how this remarkable discrimination is achieved. Kinetic proofreading mechanisms can provide the required specificity but only at the expense of much reduced sensitivity. A number of recent observations suggest that pMHC engagement of T cell receptors (TCRs) induces changes such as clustering and/or conformational alterations that enhance subsequent rebinding. We show that inclusion of induced rebinding to the same pMHC in kinetic proofreading models enhances the sensitivity of TCR recognition while retaining specificity. Moreover, induced rebinding is able to reproduce the striking, and hitherto unexplained, 2D membrane-binding properties recently reported for the TCR. |
| spellingShingle | Dushek, O Van Der Merwe, P An induced rebinding model of antigen discrimination. |
| title | An induced rebinding model of antigen discrimination. |
| title_full | An induced rebinding model of antigen discrimination. |
| title_fullStr | An induced rebinding model of antigen discrimination. |
| title_full_unstemmed | An induced rebinding model of antigen discrimination. |
| title_short | An induced rebinding model of antigen discrimination. |
| title_sort | induced rebinding model of antigen discrimination |
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