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Antagonism of cytotoxic T-lymphocyte activation by soluble CD8

Nature Medicine volume 5, pages 399–404 (1999)Cite this article

Abstract

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 CD8αα receptor, despite an extremely low affinity for MHC, inhibits activation of cytotoxic lymphocytes by obstructing CD3 ζ-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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Figure 1: Inhibition of CTL activation by sCD8αα receptor.
Figure 2: Inhibition of CTL lysis by soluble CD8αα is correlated to MHC affinity.
Figure 3: Effect of sCD8αα on early protein tyrosine phosphorylation events in CD8-dependent and independent CTLs.
Figure 4: Sedimentation analysis of sCD8αα shows no indication of multimers.

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Acknowledgements

We thank A. van der Merwe, B. Willcox and J. Wyer for sharing unpublished results; S. Davis and C. O'Callaghan for suggestions and critical review; R. Tan for the gift of clone 10; and P. Easterbrook, B. Gazzard and P. Giangrande for providing patient samples. This work was supported by the Wellcome Trust and the Medical Research Council.

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  1. Ulrich C. Gerth and David A. Price: U.C.G and D.A.P. contributed equally to this work

Authors and Affiliations

  1. Nuffield Department of Clinical Medicine, Molecular Immunology Group, Institute of Molecular Medicine, University of Oxford John Radcliffe Hospital, Headington, OX3 9DS, Oxford, UK

    Andrew K. Sewell, Ulrich C. Gerth, David A. Price, Marco A. Purbhoo, Jonathan M. Boulter, George F. Gao, John I. Bell, Rodney E. Phillips & Bent K. Jakobsen

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Correspondence to Bent K. Jakobsen.

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Sewell, A., Gerth, U., Price, D. et al. Antagonism of cytotoxic T-lymphocyte activation by soluble CD8. Nat Med 5, 399–404 (1999). https://doi.org/10.1038/7398

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