SEEKER: A genome-scale library-on-library screening platform for deciphering T cell recognition of antigen

  1. Sicheng Li
  2. Li Lin
  3. Wenxu Wu
  4. Binwen Liu
  5. Huihui Ji
  6. Zongyu Guo
  7. Yaqiong Liu
  8. Juncheng Wu
  9. Bo Liu
  10. Lisang Zhong
  11. Xiaowo Wang
  12. Huji Xu
  13. Hai Qi
Read the full article See related articles

Listed in

This article is not in any list yet, why not save it to one of your lists.
Log in to save this article

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.

Article activity feed

  1. Mentioned by @rridrobot.bsky.social on Bluesky

    Authors used pL-CRISPR.EFS.PAC from @addgene.bsky.social in their study. Including #RRIDs will make this less ambiguous. SciScore made a table with this resource, see “Automated Services” module (download as csv, xml or #jats) #RRID #STMpublishing

  2. Mentioned by @asimresearcher.bsky.social on Bluesky

    SEEKER: A genome-scale library-on-library screening platform for deciphering T cell recognition of antigen https://www.biorxiv.org/content/10.64898/2026.09.25.753432v1

  3. Version published to 10.64898/2026.09.25.753432v2 on bioRxiv
  4. Mentioned by @biorxiv-immuno.bsky.social on Bluesky

    SEEKER: A genome-scale library-on-library screening platform for deciphering T cell recognition of antigen https://www.biorxiv.org/content/10.64898/2026.09.25.753432v1

  5. Mentioned by @biorxivpreprint.bsky.social on Bluesky

    SEEKER: A genome-scale library-on-library screening platform for deciphering T cell recognition of antigen https://www.biorxiv.org/content/10.64898/2026.09.25.753432v1

  6. Version published to 10.64898/2026.09.25.753432v1 on bioRxiv