Peptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation.
Recent experiments defining T cell agonists, partial agonists and antagonists have suggested that the T cell can discriminate between subtle differences in interactions leading to T cell activation. To further understand the complexities of T cell activation, we have analyzed the requirements for th...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1997
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| _version_ | 1826269169229758464 |
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| author | Bachmann, M Oxenius, A Speiser, D Mariathasan, S Hengartner, H Zinkernagel, R Ohashi, P |
| author_facet | Bachmann, M Oxenius, A Speiser, D Mariathasan, S Hengartner, H Zinkernagel, R Ohashi, P |
| author_sort | Bachmann, M |
| collection | OXFORD |
| description | Recent experiments defining T cell agonists, partial agonists and antagonists have suggested that the T cell can discriminate between subtle differences in interactions leading to T cell activation. To further understand the complexities of T cell activation, we have analyzed the requirements for the induction of a variety of effector functions using naive T cells and a variety of altered peptide ligands. Using a strong agonist peptide, massive T cell receptor (TCR) down-regulation correlated with a wide range of effector functions that were all induced above the same threshold peptide concentration. Interestingly, the kinetics of TCR down-regulation correlated with the concentration of the peptide, whereas the maximal degree of TCR down-regulation correlated with the induction of all monitored effector functions. A selected group of altered peptide ligands was also examined that were able to render target cells susceptible for lysis by effector cytotoxic T lymphocytes. The extent of TCR down-regulation induced by these peptides corresponded to the induction of a subset of effector functions. These studies have shown that the extent of TCR down-regulation defines the strength of TCR-mediated "signal 1" which correlates with the spectrum of effector functions activated within the T cell. Thus, activation of different T cell functions requires the triggering of distinct numbers of TCR. The different parameters that influence TCR down-regulation define important distinctions between our results and previously reported findings with T cell clones and may outline decisive parameters for the consequences of T cell activation in vivo. |
| first_indexed | 2024-03-06T21:20:51Z |
| format | Journal article |
| id | oxford-uuid:416528bc-6638-4973-be70-9b5e321b21a4 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:20:51Z |
| publishDate | 1997 |
| record_format | dspace |
| spelling | oxford-uuid:416528bc-6638-4973-be70-9b5e321b21a42022-03-26T14:43:23ZPeptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:416528bc-6638-4973-be70-9b5e321b21a4EnglishSymplectic Elements at Oxford1997Bachmann, MOxenius, ASpeiser, DMariathasan, SHengartner, HZinkernagel, ROhashi, PRecent experiments defining T cell agonists, partial agonists and antagonists have suggested that the T cell can discriminate between subtle differences in interactions leading to T cell activation. To further understand the complexities of T cell activation, we have analyzed the requirements for the induction of a variety of effector functions using naive T cells and a variety of altered peptide ligands. Using a strong agonist peptide, massive T cell receptor (TCR) down-regulation correlated with a wide range of effector functions that were all induced above the same threshold peptide concentration. Interestingly, the kinetics of TCR down-regulation correlated with the concentration of the peptide, whereas the maximal degree of TCR down-regulation correlated with the induction of all monitored effector functions. A selected group of altered peptide ligands was also examined that were able to render target cells susceptible for lysis by effector cytotoxic T lymphocytes. The extent of TCR down-regulation induced by these peptides corresponded to the induction of a subset of effector functions. These studies have shown that the extent of TCR down-regulation defines the strength of TCR-mediated "signal 1" which correlates with the spectrum of effector functions activated within the T cell. Thus, activation of different T cell functions requires the triggering of distinct numbers of TCR. The different parameters that influence TCR down-regulation define important distinctions between our results and previously reported findings with T cell clones and may outline decisive parameters for the consequences of T cell activation in vivo. |
| spellingShingle | Bachmann, M Oxenius, A Speiser, D Mariathasan, S Hengartner, H Zinkernagel, R Ohashi, P Peptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation. |
| title | Peptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation. |
| title_full | Peptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation. |
| title_fullStr | Peptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation. |
| title_full_unstemmed | Peptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation. |
| title_short | Peptide-induced T cell receptor down-regulation on naive T cells predicts agonist/partial agonist properties and strictly correlates with T cell activation. |
| title_sort | peptide induced t cell receptor down regulation on naive t cells predicts agonist partial agonist properties and strictly correlates with t cell activation |
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