J Zou1, H Appel, M Rudwaleit, A Thiel, J Sieper. 1. Department of Gastroenterology and Rheumatology, Charité Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.
Abstract
BACKGROUND: CD4+ T cell responses to the G1 domain of aggrecan in patients with ankylosing spondylitis (AS) were recently reported. Whether such an immune response can be seen in the CD8+ subpopulation has not yet been determined. OBJECTIVE: To determine if HLA-B27 restricted G1-specific CD8+ T cells are present in AS and to analyse immunodominant CD8+ T cell epitopes. METHODS: Peripheral blood mononuclear cells of 45 patients with AS were stimulated with overlapping 18-mer peptides covering the whole G1 protein. Results were compared with those for patients with rheumatoid arthritis (RA) and healthy controls. For epitope analysis, G1-specific interferon gamma positive (IFNgamma+) T cells were isolated by magnetic activated cell sorting. After in vitro expansion, CD8+ T cells were restimulated with 14 subpools of G1 peptides. T cells responding to G1 peptide subpools were quantified by flow cytometry according to IFNgamma secretion. Predicted peptides were subsequently confirmed by stimulation with single peptides. RESULTS: G1-specific CD8+ T cell responses were found in 29/45 (64%) patients with AS, 18/35 (51%) patients with RA, but not in healthy controls. Five CD8+ T cell epitopes were identified as immunodominant in five patients. However, the T cell response was not HLA-B27 restricted. Nonamer peptides with an HLA-B27 binding motif did not induce a T cell response. CONCLUSION: A G1 peptide-specific CD8+ T cell response is present in AS but also in patients with RA. It does not seem to be HLA-B27 restricted. Whether such a response has a role in the pathogenesis of AS needs clarification.
BACKGROUND:CD4+ T cell responses to the G1 domain of aggrecan in patients with ankylosing spondylitis (AS) were recently reported. Whether such an immune response can be seen in the CD8+ subpopulation has not yet been determined. OBJECTIVE: To determine if HLA-B27 restricted G1-specific CD8+ T cells are present in AS and to analyse immunodominant CD8+ T cell epitopes. METHODS: Peripheral blood mononuclear cells of 45 patients with AS were stimulated with overlapping 18-mer peptides covering the whole G1 protein. Results were compared with those for patients with rheumatoid arthritis (RA) and healthy controls. For epitope analysis, G1-specific interferon gamma positive (IFNgamma+) T cells were isolated by magnetic activated cell sorting. After in vitro expansion, CD8+ T cells were restimulated with 14 subpools of G1 peptides. T cells responding to G1 peptide subpools were quantified by flow cytometry according to IFNgamma secretion. Predicted peptides were subsequently confirmed by stimulation with single peptides. RESULTS: G1-specific CD8+ T cell responses were found in 29/45 (64%) patients with AS, 18/35 (51%) patients with RA, but not in healthy controls. Five CD8+ T cell epitopes were identified as immunodominant in five patients. However, the T cell response was not HLA-B27 restricted. Nonamer peptides with an HLA-B27 binding motif did not induce a T cell response. CONCLUSION: A G1 peptide-specific CD8+ T cell response is present in AS but also in patients with RA. It does not seem to be HLA-B27 restricted. Whether such a response has a role in the pathogenesis of AS needs clarification.
Authors: Y Zhang; A Guerassimov; J Y Leroux; A Cartman; C Webber; R Lalic; E de Miguel; L C Rosenberg; A R Poole Journal: J Clin Invest Date: 1998-04-15 Impact factor: 14.808
Authors: E I Buzás; F R Brennan; K Mikecz; M Garzó; G Negroiu; K Holló; G Cs-Szabó; E Pintye; T T Glant Journal: J Immunol Date: 1995-09-01 Impact factor: 5.422
Authors: Sylvia Kamphuis; Kolbrún Hrafnkelsdóttir; Mark R Klein; Wilco de Jager; Margje H Haverkamp; Jolanda H M van Bilsen; Salvatore Albani; Wietse Kuis; Marca H M Wauben; Berent J Prakken Journal: Arthritis Res Ther Date: 2006 Impact factor: 5.156