Antagonism of cytotoxic T-lymphocyte activation by soluble CD8.

The CD8 co-receptor is important in the differentiation and selection of class I MHC-restricted T cells during thymic development, and in the activation of mature T lymphocytes in response to antigen. Here we show that soluble CD8alphaalpha receptor, despite an extremely low affinity for MHC, inhibi...

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Main Authors: Sewell, A, Gerth, U, Price, D, Purbhoo, M, Boulter, J, Gao, G, Bell, J, Phillips, R, Jakobsen, B
Format: Journal article
Language:English
Published: 1999
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author Sewell, A
Gerth, U
Price, D
Purbhoo, M
Boulter, J
Gao, G
Bell, J
Phillips, R
Jakobsen, B
author_facet Sewell, A
Gerth, U
Price, D
Purbhoo, M
Boulter, J
Gao, G
Bell, J
Phillips, R
Jakobsen, B
author_sort Sewell, A
collection OXFORD
description The CD8 co-receptor is important in the differentiation and selection of class I MHC-restricted T cells during thymic development, and in the activation of mature T lymphocytes in response to antigen. Here we show that soluble CD8alphaalpha receptor, despite an extremely low affinity for MHC, inhibits activation of cytotoxic lymphocytes by obstructing CD3 zeta-chain phosphorylation. We propose a model for this effect that involves interference of productive receptor multimerization at the T-cell surface. These results provide new insights into the mechanism of T-cell activation and evidence that CD8 function is exquisitely sensitive to disruption, an effect that might be exploited by molecular therapeutics.
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spelling oxford-uuid:bbed70f3-c01d-4cd1-b7e9-98776b8edd3a2022-03-27T05:20:34ZAntagonism of cytotoxic T-lymphocyte activation by soluble CD8.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:bbed70f3-c01d-4cd1-b7e9-98776b8edd3aEnglishSymplectic Elements at Oxford1999Sewell, AGerth, UPrice, DPurbhoo, MBoulter, JGao, GBell, JPhillips, RJakobsen, BThe CD8 co-receptor is important in the differentiation and selection of class I MHC-restricted T cells during thymic development, and in the activation of mature T lymphocytes in response to antigen. Here we show that soluble CD8alphaalpha receptor, despite an extremely low affinity for MHC, inhibits activation of cytotoxic lymphocytes by obstructing CD3 zeta-chain phosphorylation. We propose a model for this effect that involves interference of productive receptor multimerization at the T-cell surface. These results provide new insights into the mechanism of T-cell activation and evidence that CD8 function is exquisitely sensitive to disruption, an effect that might be exploited by molecular therapeutics.
spellingShingle Sewell, A
Gerth, U
Price, D
Purbhoo, M
Boulter, J
Gao, G
Bell, J
Phillips, R
Jakobsen, B
Antagonism of cytotoxic T-lymphocyte activation by soluble CD8.
title Antagonism of cytotoxic T-lymphocyte activation by soluble CD8.
title_full Antagonism of cytotoxic T-lymphocyte activation by soluble CD8.
title_fullStr Antagonism of cytotoxic T-lymphocyte activation by soluble CD8.
title_full_unstemmed Antagonism of cytotoxic T-lymphocyte activation by soluble CD8.
title_short Antagonism of cytotoxic T-lymphocyte activation by soluble CD8.
title_sort antagonism of cytotoxic t lymphocyte activation by soluble cd8
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