Details

Autor(en) / Beteiligte

• Yang, Xinbo
• Garner, Lee I
• Zvyagin, Ivan V
• Paley, Michael A
• Komech, Ekaterina A
• Jude, Kevin M
• Zhao, Xiang
• Fernandes, Ricardo A
• Hassman, Lynn M
• Paley, Grace L
• Savvides, Christina S
• Brackenridge, Simon
• Quastel, Max N
• Chudakov, Dmitriy M
• Bowness, Paul
• Yokoyama, Wayne M
• McMichael, Andrew J
• Gillespie, Geraldine M
• Garcia, K Christopher

Titel

Autoimmunity-associated T cell receptors recognize HLA-B27-bound peptides

Ist Teil von

• Nature (London), 2022-12, Vol.612 (7941), p.771-777

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• Human leucocyte antigen B*27 (HLA-B*27) is strongly associated with inflammatory diseases of the spine and pelvis (for example, ankylosing spondylitis (AS)) and the eye (that is, acute anterior uveitis (AAU)) . How HLA-B*27 facilitates disease remains unknown, but one possible mechanism could involve presentation of pathogenic peptides to CD8 T cells. Here we isolated orphan T cell receptors (TCRs) expressing a disease-associated public β-chain variable region-complementary-determining region 3β (BV9-CDR3β) motif from blood and synovial fluid T cells from individuals with AS and from the eye in individuals with AAU. These TCRs showed consistent α-chain variable region (AV21) chain pairing and were clonally expanded in the joint and eye. We used HLA-B*27:05 yeast display peptide libraries to identify shared self-peptides and microbial peptides that activated the AS- and AAU-derived TCRs. Structural analysis revealed that TCR cross-reactivity for peptide-MHC was rooted in a shared binding motif present in both self-antigens and microbial antigens that engages the BV9-CDR3β TCRs. These findings support the hypothesis that microbial antigens and self-antigens could play a pathogenic role in HLA-B*27-associated disease.