HLA-B27-restricted T cells from patients with ankylosing spondylitis recognize peptides from B*2705 that are similar to bacteria-derived peptides

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Abstract
Ankylosing spondylitis (AS) is an inflammatory systemic disease affecting the spine, sacroiliacal and peripheral joints. Although the aetiology of AS remains unknown, the strong association with the HLA‐B27 allele might reflect directly a detrimental effect of the HLA‐B27 molecule itself, resulting from its potential capability to present ‘arthritogenic’ peptides to CD8+ T cells. Because some forms of SpA are triggered by enterobacterial infection, such arthritogenic peptides might originate from autologous and/or bacterial proteins triggering cross‐reactive CD8+ T cell clones. Intriguingly, two peptides from the second extracellular domain of HLA‐B*2705 share sequence homologies with several enterobacterial antigens, exhibit the HLA‐B27‐binding‐motif, and are presented by HLA‐B*2705 itself. The objective of this study was to examine the clonal T cell reactivity against these peptides in patients with AS. To this end, we screened peripheral blood lymphocytes (PBL) of 26 patients with AS and 24 healthy donors for TNF‐α‐producing cells using ELISPOT assays. PBL and synovial fluid‐derived lymphocytes (SFL) of peptide‐responsive patients were then stimulated and cultured with the relevant peptide and control peptides in vitro. Antigen‐specific T cell lines (TCL) were identified by standard chromium release assays. Clonal analysis was performed subsequently applying TCRB‐CDR3 spectratyping. Among eight peptides tested, only the HLA‐B27 168–176 peptide LRRYLENGK was recognized by PBL from B27+ AS patients but not from B27+ healthy controls (P = 0·001). LRRYLENGK‐specific T cell clones used preferentially the TCRBV5S1 and the BV14 segment. These results suggest that an HLA‐B27‐derived peptide with homology to bacterial peptides may play a role in AS.

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