{
  "abstract": "Human leukocyte antigen B*27 (HLA-B*27) is a major risk factor for autoimmune diseases such as axial spondyloarthritis (axSpA), acute anterior uveitis (AAU), and psoriatic arthritis (PsA). HLA-B*27 presents bacterial and self-antigens to disease-associated CD8+ T cells, however, how this leads to a pathogenic IL-17-mediated disease remains unclear. We performed mutational experiments in an established disease-associated TCR and demonstrated that the pathogenic motif encompasses a wider range of TCR sequences than previously appreciated. We next leveraged computational pairing of alpha/beta TCR sequencing (TCR-seq) to demonstrate that the broadened pathogenic motif distinguishes axSpA and AAU patients from healthy controls. Paired single-cell RNA sequencing and single-cell TCR sequencing datasets demonstrated that the pathogenic cells have a distinct transcriptional signature. We find a coupling of pathogenic TCRs to this transcriptional signature in public datasets from axSpA and PsA joint fluid and AAU ocular fluid. Finally, we detect the pathogenic CD8+ T cells in the gut and demonstrate that they express a Type 17 program. Our findings suggest that HLA-B*27+ axSpA, AAU, and PsA are initiated by HLA-B*27-restricted pathogenic CD8+ T cells that undergo Type 17 differentiation in response to intestinal antigens.",
  "abstract_shown": true,
  "affiliations": [
    "Washington University in St Louis"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "name": "I. Risch"
    },
    {
      "name": "Q. Wu"
    },
    {
      "name": "R. Devkota"
    },
    {
      "name": "S. Y. Li"
    },
    {
      "name": "J. Um"
    },
    {
      "name": "T. Alves Pereira Neto"
    },
    {
      "name": "S. Walden"
    },
    {
      "name": "P. H. Arantes de Faria"
    },
    {
      "name": "A. Belean"
    },
    {
      "name": "L. Durham"
    },
    {
      "name": "M. Tang"
    },
    {
      "name": "Z. Qaiyum"
    },
    {
      "name": "R. D. Inman"
    },
    {
      "name": "L. S. Taams"
    },
    {
      "name": "X. Yang"
    },
    {
      "name": "P. A. Mudd"
    },
    {
      "name": "N. Borcherding"
    },
    {
      "name": "M. Griffith"
    },
    {
      "name": "O. L. Griffith"
    },
    {
      "affs": [
        0
      ],
      "name": "M. A. Paley"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2dkhejgxs33as.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.18.752092",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752092v1.full",
  "id": "2dkhejgxs33as",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752092v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2745|Spondyloarthritis Studies and Treatments"
    ]
  ],
  "openalex": "W7214150612",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752092v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-18",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2dkhejgxs33as.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:25Z",
      "native_id": "10.64898/2026.09.18.752092",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.18.752092v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Refinement of the Pathogenic T Cell Receptor Motif Suggests Type 17 CD8+ T Cells Initiate HLA-B*27-associated Autoimmunity",
  "title_text": "Refinement of the Pathogenic T Cell Receptor Motif Suggests Type 17 CD8+ T Cells Initiate HLA-B*27-associated Autoimmunity",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:25Z",
  "url": "https://research.draconitic.com/paper/2dkhejgxs33as",
  "venue": "bioRxiv",
  "versions": []
}