Open Access Open Badges Research article

Insights into spatial configuration of a galactosylated epitope required to trigger arthritogenic T-cell receptors specific for the sugar moiety

Simon Glatigny12, Marie-Agnès Blaton12, Julien Marin3, Sylvie Mistou12, Jean-Paul Briand3, Gilles Guichard3, Catherine Fournier12 and Gilles Chiocchia12*

Author Affiliations

1 Institut Cochin, Université Paris Descartes CNRS (UMR 8104), 27 rue du Fbg Saint Jacques, Paris, F-75014, France

2 INSERM U567, Département d'Immunologie, 27 rue du Fbg Saint Jacques, Paris, F-75014, France

3 UPR 9021 CNRS – Immunologie et Chimie Thérapeutiques (ICT), Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, 67084 Strasbourg Cedex, France

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Arthritis Research & Therapy 2007, 9:R92  doi:10.1186/ar2291

Published: 11 September 2007


The immunodominant epitope of bovine type II collagen (CII256–270) in Aq mice carries a hydroxylysine-264 linked galactose (Gal-Hyl264), the recognition of which is central to the development of collagen-induced arthritis. This study explores the molecular interactions involved in the engagement of T-cell receptors (TCRs) with such epitopes. Responses of three anti-CII T-cell hybridomas and clone A9.2 (all sharing close TCR sequences) to a panel of CII256–270 analogues incorporating Gal-Hyl264 with a modified side chain were determined. Recognition of naturally occurring CII256–270 peptides by either group of T cells depended strictly upon the presence of the carbohydrate and, more precisely, its intact HO-4 group. Modifications of primary amino group on the hydroxylysine side chain eliminated T-cell reactivity, notwithstanding the presence of the galactosyl moiety. Moderate stereochemical changes, such as altered sugar orientation and methylation at the galactose anchor position, were still permissive. Conversely, robust transformations affecting the relative positions of the key elements were detrimental to TCR recognition. To conclude, these data provide strong new experimental evidence that integrity of both galactose HO-4 and hydroxylysine side chain primary amino groups are mandatory for activation of anti-Gal-Hyl264 TCRs. They also indicate that there is a certain degree of TCR plasticity in peptide-TCR interactions.