ORIGINAL ARTICLE

Cell Research (2008): 641-648
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Differential remodeling of a T-cell transcriptome following CD8- versus CD3-induced signaling

S Hussain I Abidi^1,2, Tao Dong¹, Mai T Vuong¹, Vattipally B Sreenu¹, Sarah L Rowland-Jones¹, Edward J Evans¹ and Simon J Davis¹

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

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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.

Cell Research (2008) 18:641-648. doi: 10.1038/cr.2008.56; published online 13 May 2008

Keywords: receptor triggering, signaling, CD8, coreceptor, SAGE, expression analysis