Kinetics and mechanics of two-dimensional interactions between T cell receptors and different activating ligands.
Adaptive immune responses are driven by interactions between T cell antigen receptors (TCRs) and complexes of peptide antigens (p) bound to Major Histocompatibility Complex proteins (MHC) on the surface of antigen-presenting cells. Many experiments support the hypothesis that T cell response is quan...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2012
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| _version_ | 1826277763906011136 |
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| author | Robert, P Aleksic, M Dushek, O Cerundolo, V Bongrand, P Van Der Merwe, P |
| author_facet | Robert, P Aleksic, M Dushek, O Cerundolo, V Bongrand, P Van Der Merwe, P |
| author_sort | Robert, P |
| collection | OXFORD |
| description | Adaptive immune responses are driven by interactions between T cell antigen receptors (TCRs) and complexes of peptide antigens (p) bound to Major Histocompatibility Complex proteins (MHC) on the surface of antigen-presenting cells. Many experiments support the hypothesis that T cell response is quantitatively and qualitatively dependent on the so-called strength of TCR/pMHC association. Most available data are correlations between binding parameters measured in solution (three-dimensional) and pMHC activation potency, suggesting that full lymphocyte activation required a minimal lifetime for TCR/pMHC interaction. However, recent reports suggest important discrepancies between the binding properties of ligand-receptor couples measured in solution (three-dimensional) and those measured using surface-bound molecules (two-dimensional). Other reports suggest that bond mechanical strength may be important in addition to kinetic parameters. Here, we used a laminar flow chamber to monitor at the single molecule level the two-dimensional interaction between a recombinant human TCR and eight pMHCs with variable potency. We found that 1), two-dimensional dissociation rates were comparable to three-dimensional parameters previously obtained with the same molecules; 2), no significant correlation was found between association rates and activating potency of pMHCs; 3), bond mechanical strength was partly independent of bond lifetime; and 4), a suitable combination of bond lifetime and bond strength displayed optimal correlation with activation efficiency. These results suggest possible refinements of contemporary models of signal generation by T cell receptors. In conclusion, we reported, for the first time to our knowledge, the two-dimensional binding properties of eight TCR/pMHC couples in a cell-free system with single bond resolution. |
| first_indexed | 2024-03-06T23:33:48Z |
| format | Journal article |
| id | oxford-uuid:6cf3c3b9-e70f-4264-9328-007ac89812a1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:33:48Z |
| publishDate | 2012 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:6cf3c3b9-e70f-4264-9328-007ac89812a12022-03-26T19:14:33ZKinetics and mechanics of two-dimensional interactions between T cell receptors and different activating ligands.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6cf3c3b9-e70f-4264-9328-007ac89812a1Molecular biophysics (biochemistry)ImmunologyEnglishSymplectic Elements at OxfordElsevier2012Robert, PAleksic, MDushek, OCerundolo, VBongrand, PVan Der Merwe, PAdaptive immune responses are driven by interactions between T cell antigen receptors (TCRs) and complexes of peptide antigens (p) bound to Major Histocompatibility Complex proteins (MHC) on the surface of antigen-presenting cells. Many experiments support the hypothesis that T cell response is quantitatively and qualitatively dependent on the so-called strength of TCR/pMHC association. Most available data are correlations between binding parameters measured in solution (three-dimensional) and pMHC activation potency, suggesting that full lymphocyte activation required a minimal lifetime for TCR/pMHC interaction. However, recent reports suggest important discrepancies between the binding properties of ligand-receptor couples measured in solution (three-dimensional) and those measured using surface-bound molecules (two-dimensional). Other reports suggest that bond mechanical strength may be important in addition to kinetic parameters. Here, we used a laminar flow chamber to monitor at the single molecule level the two-dimensional interaction between a recombinant human TCR and eight pMHCs with variable potency. We found that 1), two-dimensional dissociation rates were comparable to three-dimensional parameters previously obtained with the same molecules; 2), no significant correlation was found between association rates and activating potency of pMHCs; 3), bond mechanical strength was partly independent of bond lifetime; and 4), a suitable combination of bond lifetime and bond strength displayed optimal correlation with activation efficiency. These results suggest possible refinements of contemporary models of signal generation by T cell receptors. In conclusion, we reported, for the first time to our knowledge, the two-dimensional binding properties of eight TCR/pMHC couples in a cell-free system with single bond resolution. |
| spellingShingle | Molecular biophysics (biochemistry) Immunology Robert, P Aleksic, M Dushek, O Cerundolo, V Bongrand, P Van Der Merwe, P Kinetics and mechanics of two-dimensional interactions between T cell receptors and different activating ligands. |
| title | Kinetics and mechanics of two-dimensional interactions between T cell receptors and different activating ligands. |
| title_full | Kinetics and mechanics of two-dimensional interactions between T cell receptors and different activating ligands. |
| title_fullStr | Kinetics and mechanics of two-dimensional interactions between T cell receptors and different activating ligands. |
| title_full_unstemmed | Kinetics and mechanics of two-dimensional interactions between T cell receptors and different activating ligands. |
| title_short | Kinetics and mechanics of two-dimensional interactions between T cell receptors and different activating ligands. |
| title_sort | kinetics and mechanics of two dimensional interactions between t cell receptors and different activating ligands |
| topic | Molecular biophysics (biochemistry) Immunology |
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