Analysis of the CD8+ T cell response to the G1 domain of aggrecan in ankylosing spondylitis. Issue 5 (11th November 2004)

• Record Type: Journal Article
• Authors: Zou, J; Appel, H; Rudwaleit, M; Thiel, A; Sieper, J
• Is Part Of: Annals of the rheumatic diseases. Volume 64:Issue 5(2005)
• Page Start: 722
• Page End: 729
• Publication Date: 2004-11-11
• Subjects: AA, amino acid -- AS, ankylosing spondylitis -- IFNγ, interferon γ -- IL, interleukin -- MACS, magnetic activated cell sorting -- PB, peripheral blood -- PBMCs, peripheral blood mononuclear cells -- RA, rheumatoid arthritis -- SEB, Staphylococcus enterotoxin B -- TNFα, tumour necrosis factor α; CD8+ T cells -- aggrecan -- ankylosing spondylitis -- self antigens; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2004.024455
• Languages: English
• ISSNs: 0003-4967

Abstract

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 (IFNγ+) 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 IFNγ 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.