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CD8 engagement with class I major histocompatibility antigens greatly enhances T-cell activation, but it is not clear how this is achieved. We address the question of whether or not the antibody-mediated ligation of CD8 alone induces transcriptional remodeling in a T-cell clone, using serial analysis of gene expression. Even though it fails to induce overt phenotypic changes, we find that CD8 ligation profoundly alters transcription in the T-cell clone, at a scale comparable to that induced by antibody-mediated ligation of CD3. The character of the resulting changes is distinct, however, with the net effect of CD8 ligation being substantially inhibitory. We speculate that ligating CD8 induces weak, T-cell receptor (TCR)-mediated inhibitory signals reminiscent of the effects of TCR antagonists. Our results imply that CD8 ligation alone is incapable of activating the T-cell clone because it fails to fully induce NFAT-dependent transcription.

Original publication

DOI

10.1038/cr.2008.56

Type

Journal article

Journal

Cell research

Publication Date

06/2008

Volume

18

Pages

641 - 648

Addresses

Nuffield Department of Clinical Medicine and MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.

Keywords

T-Lymphocytes, Clone Cells, RNA, Messenger, Antibodies, Gene Expression Profiling, Signal Transduction, Gene Expression Regulation, Gene Library, CD8 Antigens, CD3 Complex