Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation.
Efficient T cell activation requires the engagement of a variety of ligand/receptor molecules in addition to T cell receptor (TCR)-major histocompatibility complex (MHC)/peptide interactions. The leukocyte function antigen 1 (LFA-1) and the CD28 glycoprotein have both been implicated in T cell activ...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1997
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| _version_ | 1797100038646661120 |
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| author | Bachmann, M McKall-Faienza, K Schmits, R Bouchard, D Beach, J Speiser, D Mak, T Ohashi, P |
| author_facet | Bachmann, M McKall-Faienza, K Schmits, R Bouchard, D Beach, J Speiser, D Mak, T Ohashi, P |
| author_sort | Bachmann, M |
| collection | OXFORD |
| description | Efficient T cell activation requires the engagement of a variety of ligand/receptor molecules in addition to T cell receptor (TCR)-major histocompatibility complex (MHC)/peptide interactions. The leukocyte function antigen 1 (LFA-1) and the CD28 glycoprotein have both been implicated in T cell activation. The present study dissects the roles of LFA-1 and CD28 in the activation of naive virus-specific CD8+ T cells. We demonstrate that LFA-1 facilitates T cell activation by lowering the amounts of antigen necessary for T cell activation. In the absence of LFA-1, 100-fold more antigen was required for T cell-antigen-presenting cell (APC) conjugation and all subsequent events of T cell activation, including TCR down-regulation, Ca2+-flux, T cell proliferation, and lytic effector cell induction. Thus, LFA-1 facilitates the functional triggering of TCRs by promoting adhesion of T cells to APCs but does not affect T cell activation otherwise. In contrast, CD28 played an entirely different role during T cell activation. CD28 reduced the number of TCRs that had to be triggered for T cell activation and allowed activation of T cells by low affinity ligands. CD28 but not LFA-1 prevented induction of T cell unresponsiveness after stimulation of TCRs. These results demonstrate that LFA-1 and CD28 exhibit distinct, nonoverlapping ways to influence T cell activation and suggest that the terms costimulation and signal 2 should be revisited. |
| first_indexed | 2024-03-07T05:32:05Z |
| format | Journal article |
| id | oxford-uuid:e29beebd-986b-481d-a954-f8ffe9fba836 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:32:05Z |
| publishDate | 1997 |
| record_format | dspace |
| spelling | oxford-uuid:e29beebd-986b-481d-a954-f8ffe9fba8362022-03-27T10:02:41ZDistinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e29beebd-986b-481d-a954-f8ffe9fba836EnglishSymplectic Elements at Oxford1997Bachmann, MMcKall-Faienza, KSchmits, RBouchard, DBeach, JSpeiser, DMak, TOhashi, PEfficient T cell activation requires the engagement of a variety of ligand/receptor molecules in addition to T cell receptor (TCR)-major histocompatibility complex (MHC)/peptide interactions. The leukocyte function antigen 1 (LFA-1) and the CD28 glycoprotein have both been implicated in T cell activation. The present study dissects the roles of LFA-1 and CD28 in the activation of naive virus-specific CD8+ T cells. We demonstrate that LFA-1 facilitates T cell activation by lowering the amounts of antigen necessary for T cell activation. In the absence of LFA-1, 100-fold more antigen was required for T cell-antigen-presenting cell (APC) conjugation and all subsequent events of T cell activation, including TCR down-regulation, Ca2+-flux, T cell proliferation, and lytic effector cell induction. Thus, LFA-1 facilitates the functional triggering of TCRs by promoting adhesion of T cells to APCs but does not affect T cell activation otherwise. In contrast, CD28 played an entirely different role during T cell activation. CD28 reduced the number of TCRs that had to be triggered for T cell activation and allowed activation of T cells by low affinity ligands. CD28 but not LFA-1 prevented induction of T cell unresponsiveness after stimulation of TCRs. These results demonstrate that LFA-1 and CD28 exhibit distinct, nonoverlapping ways to influence T cell activation and suggest that the terms costimulation and signal 2 should be revisited. |
| spellingShingle | Bachmann, M McKall-Faienza, K Schmits, R Bouchard, D Beach, J Speiser, D Mak, T Ohashi, P Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation. |
| title | Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation. |
| title_full | Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation. |
| title_fullStr | Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation. |
| title_full_unstemmed | Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation. |
| title_short | Distinct roles for LFA-1 and CD28 during activation of naive T cells: adhesion versus costimulation. |
| title_sort | distinct roles for lfa 1 and cd28 during activation of naive t cells adhesion versus costimulation |
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