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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.

Original publication

DOI

10.1038/7398

Type

Journal article

Journal

Nat Med

Publication Date

04/1999

Volume

5

Pages

399 - 404

Keywords

CD3 Complex, CD8 Antigens, Dimerization, Histocompatibility Antigens Class I, Ligands, Lymphocyte Activation, Major Histocompatibility Complex, Models, Immunological, Peptides, Phosphorylation, Protein Conformation, Receptors, Antigen, T-Cell, Signal Transduction, Solubility, T-Lymphocytes, Cytotoxic