{
  "abstract": "Decoding which antigens activate a given T cell receptor (TCR) is a central challenge in immunology. We present SEEKER, a functional genome-scale library-on-library screening platform built on three elements: a Jurkat-derived T-APC cell (TAPCell) that combinatorially expresses one TCR and one peptide-MHC drawn from separate libraries together with an NFAT activation reporter; encapsulation of single TAPCells in a thermos-reversible hydrogel for isolated clonal expansion, so recognition is read out as intraclonal activation; and dual-asymmetric PCR that links TCR- and pMHC-encoding sequences into a heritable unit, enabling progressive hit enrichment over screening rounds. SEEKER interrogates ~10^8 TCR-pMHC combinations per run without prior knowledge. Screening joint-infiltrating CD8+ T cells from HLA-B*27+ ankylosing spondylitis patients against proteome-wide libraries validated 53 TCR-peptide pairs, uncovered extensive cross-recognition of self and common viral epitopes, and revealed highly polyreactive T cells recognizing up to 80 autoantigens, implicating virus-triggered poly-autoreactivity in multi-organ autoimmune diseases.",
  "abstract_shown": true,
  "affiliations": [
    "School of Basic Medical Sciences, Tsinghua Medicine, Tsinghua University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "S. Li"
    },
    {
      "name": "L. Lin"
    },
    {
      "name": "W. Wu"
    },
    {
      "name": "B. Liu"
    },
    {
      "name": "H. Ji"
    },
    {
      "name": "Z. Guo"
    },
    {
      "name": "Y. Liu"
    },
    {
      "name": "J. Wu"
    },
    {
      "name": "B. Liu"
    },
    {
      "name": "L. Zhong"
    },
    {
      "name": "X. Wang"
    },
    {
      "name": "H. Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "H. Qi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1dpb57k0bt1cc.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.753432",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.753432v1.full",
  "id": "1dpb57k0bt1cc",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.753432v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7215052002",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.753432v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1dpb57k0bt1cc.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:42Z",
      "native_id": "10.64898/2026.09.25.753432",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.753432v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "SEEKER: A genome-scale library-on-library screening platform for deciphering T cell recognition of antigen",
  "title_text": "SEEKER: A genome-scale library-on-library screening platform for deciphering T cell recognition of antigen",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:56Z",
  "url": "https://research.draconitic.com/paper/1dpb57k0bt1cc",
  "venue": "bioRxiv",
  "versions": []
}