1. ¹Nuffield 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;
2. ²Present address: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA

Correspondence: Edward J Evans, Tel: +44-1865-221336; E-mail: edward.evans@ndm.ox.ac.uk; Simon J Davis, Tel: +44-1865-221336; E-mail: simon.davis@ndm.ox.ac.uk

Received 28 August 2007; Revised 13 December 2007; Accepted 18 January 2008.

Abstract

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.