{
  "id": 11333883,
  "title": "SEEKER: A genome-scale library-on-library screening platform for deciphering T cell recognition of antigen",
  "url": "https://urgent.news/2026/10/01/seeker-a-genome-scale-library-on-library-screening-platform-for",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-01T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.753432v1?rss=1"
  },
  "original_language": "en",
  "account": "Deciphering which antigens activate T cell receptors (TCRs) is a crucial challenge in immunology, and researchers have now introduced SEEKER, a groundbreaking platform to address this issue. This innovative system comprises three key components: a Jurkat-derived T-APC cell (referred to as TAPCell) that simultaneously expresses a TCR and a peptide-MHC (pMHC) combination from separate libraries, alongside an NFAT activation reporter.\n\nTo ensure isolated clonal expansion, the TAPCells are encapsulated within a thermos-reversible hydrogel. This allows for the accurate reading of recognition as intraclonal activation. Additionally, dual-asymmetric PCR plays a pivotal role by linking TCR- and pMHC-encoding sequences into a heritable unit. This enables progressive enrichment of hits throughout the screening process, even without prior knowledge of the specific antigens being targeted.\n\nThe SEEKER platform is capable of interrogating an astounding ~10^8 TCR-pMHC combinations per run, making it an incredibly powerful tool in the field. In a recent case study, the platform was applied to screen joint-infiltrating CD8+ T cells from HLA-B*27+ ankylosing spondylitis patients against proteome-wide libraries. This screening process successfully validated 53 TCR-peptide pairs, revealing extensive cross-recognition of both self and common viral epitopes. More importantly, the study uncovered highly polyreactive T cells that recognize up to 80 autoantigens, shedding light on the role of virus-triggered poly-autoreactivity in multi-organ autoimmune diseases.",
  "summary": "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…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}