7N2O

AS4.2-YEIH-HLA*B27

Summary for 7N2O

• Entry DOI: 10.2210/pdb7n2o/pdb
• Descriptor: YeiH protein, Human leukocyte antigen (HLA) B27, Beta-2-microglobulin, ... (8 entities in total)
• Functional Keywords: tcr mhc hla-b27, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 96072.23

Authors

Yang, X.,Jude, K.M.,Garcia, K.C. (deposition date: 2021-05-29, release date: 2022-12-07, Last modification date: 2024-11-06)

Primary citation

Yang, X.,Garner, L.I.,Zvyagin, I.V.,Paley, M.A.,Komech, E.A.,Jude, K.M.,Zhao, X.,Fernandes, R.A.,Hassman, L.M.,Paley, G.L.,Savvides, C.S.,Brackenridge, S.,Quastel, M.N.,Chudakov, D.M.,Bowness, P.,Yokoyama, W.M.,McMichael, A.J.,Gillespie, G.M.,Garcia, K.C.
Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides.
Nature, 612:771-777, 2022

PubMed Abstract: 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.

PubMed: 36477533
DOI: 10.1038/s41586-022-05501-7

Experimental method

X-RAY DIFFRACTION (2.3 Å)