CD8(+) T-cell autoreactivity to an HLA-B27-restricted self-epitope correlates with ankylosing spondylitis.
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-gamma 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.
Fiorillo
M T
MT
Department of Cell Biology and Development, University of Rome "La Sapienza", Rome, Italy.
Maragno
M
M
Butler
R
R
Dupuis
M L
ML
Sorrentino
R
R
D017951:Antigen Presentation; D015551:Autoimmunity; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D015796:HLA-B27 Antigen / Q000502:physiology*; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology; D018005:Receptors, Vasoactive Intestinal Peptide / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000209:etiology / Q000276:immunology*
D000939:Epitopes; D015796:HLA-B27 Antigen; D010446:Peptide Fragments; D018005:Receptors, Vasoactive Intestinal Peptide