Analysis of the CD8+ T cell response to the G1 domain of aggrecan in ankylosing spondylitis.

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.

• Authors: J Zou, H Appel, M Rudwaleit, A Thiel, J Sieper
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 64 Issue 5 Pg. 722-9 (May 2005) ISSN: 0003-4967 [Print] England
• PMID: 15539415 (Publication Type: Journal Article)

Chemical References

• Aggrecans
• Epitopes, T-Lymphocyte
• Extracellular Matrix Proteins
• HLA-B27 Antigen
• Immunodominant Epitopes
• Lectins, C-Type
• Proteoglycans
• Interferon-gamma

Topics

• Adult
• Aggrecans
• Arthritis, Rheumatoid (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cells, Cultured
• Epitopes, T-Lymphocyte (immunology)
• Extracellular Matrix Proteins (immunology)
• Flow Cytometry
• HLA-B27 Antigen (analysis)
• Humans
• Immunodominant Epitopes (immunology)
• Interferon-gamma (blood)
• Lectins, C-Type
• Lymphocyte Activation (immunology)
• Middle Aged
• Proteoglycans (immunology)
• Spondylitis, Ankylosing (immunology)