CD8+ T-cell autoreactivity to an HLA-B27–restricted self-epitope correlates with ankylosing spondylitis
Maria T. Fiorillo, Monica Maragno, Richard Butler, Maria L. Dupuis, Rosa Sorrentino
Maria T. Fiorillo, Monica Maragno, Richard Butler, Maria L. Dupuis, Rosa Sorrentino
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CD8+ T-cell autoreactivity to an HLA-B27–restricted self-epitope correlates with ankylosing spondylitis

Abstract

HLA-B27 is highly associated with ankylosing spondylitis (AS), but the mechanism is unknown. Among the HLA-B27 alleles, B*2709, which differs by one amino acid from the susceptible B*2705, is not associated with the disease. Here, we analyze the reactivity, in patients with AS and in healthy controls carrying the B*2709 or B*2705 alleles, to an EBV epitope derived from LMP2 (236-244) and to a sequence-related self-peptide from vasoactive intestinal peptide receptor 1 (VIP1R 400-408). We found that both B*2705+ and B*2709+ subjects possess LMP2 236-244–specific, HLA-B27–restricted T cells, whereas only the B*2705+ individuals respond significantly to VIP1R 400-408. These results prompted us to compare, by IFN-γ ELISPOT analysis, the T-cell response to VIP1R 400-408 in patients with AS versus B*2705 healthy controls. The data show that VIP1R 400-408–specific reactivity is a major feature of the patients with AS. These findings show, for the first time to our knowledge, a widespread reactivity in patients with AS against a self-epitope that exhibits some features of a putative “arthritogenic” peptide.

Authors

Maria T. Fiorillo, Monica Maragno, Richard Butler, Maria L. Dupuis, Rosa Sorrentino

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Frequency of VIP1R and LMP2 T-cell responders evaluated by IFN-γ ELISPOT...
Frequency of VIP1R and LMP2 T-cell responders evaluated by IFN-γ ELISPOT assay. Enumeration of IFN-γ spot-forming cells (SFCs) in a 10-day ELISPOT assay performed with peptide-restimulated PBMCs from eight patients with AS and in ten B*2705+ healthy subjects. (a) VIP1R 400-408; (b) LMP2 236-244; (c) NP 383-391 from influenza nucleoprotein; (d) H2 325-333 from TIS 11B; and (e) p53 266-274. For some individuals, the reactivity to control peptides (flu NP, H2, and p53) was not tested because of limited number of cells. ND, not done. Values are reported as the number of IFN-γ SFCs from peptide-restimulated PBMCs minus the number of IFN-γ SFCs from medium-grown PBMCs per 106 PBMCs. Comparison of the frequency of VIP1R- and LMP2-responder T cells between patients with AS and healthy controls was performed using the two-tailed nonparametric Mann-Whitney test (25). VIP1R 400-408: P = 0.0003; LMP2 236-244: P = 0.04.