{
  "abstract": "MHC restriction -- the requirement for {beta} T cell receptors (TCRs) to recognize Major Histocompatibility Complex (MHC) molecules when presenting peptide antigens -- is a pillar of adaptive immunity. Here, we provide direct structural evidence for TCR germline-encoded recognition of MHC molecules irrespective of antigenic peptide. We engineered \"germline-like\" TCRs to eliminate CDR3 specificity for peptide, and a molecular clamping strategy to trap ultra-low-affinity complexes with peptide-MHC for cryo-EM. We find that germline-like TCR/pMHC docking modes are identical to wild-type T cell receptors with intact CDR3 loops, across distinct peptide antigens and MHC alleles. Analysis of human TCR repertoires reveals enrichment of specific V genes and V-V{beta} pairing patterns associated with HLA-A*02 contexts. Thus, the TCR germline encodes the blueprint for MHC restriction, providing a sequence-based framework that could inform computational and AI-driven prediction of TCR specificity.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University School of Medicine; Howard Hughes Medical Institute"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "name": "N. Wang"
    },
    {
      "name": "M. T. Borowska"
    },
    {
      "name": "K. M. Jude"
    },
    {
      "name": "X. Chen"
    },
    {
      "name": "C. Wang"
    },
    {
      "name": "X. Xiang"
    },
    {
      "name": "L. D. Liu"
    },
    {
      "name": "R. Ma"
    },
    {
      "name": "A. Motiani"
    },
    {
      "name": "S. C. Wilson"
    },
    {
      "name": "W. Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "K. C. Garcia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/72zvrwbswrmhw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.24.754241",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754241v1.full",
  "id": "72zvrwbswrmhw",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754241v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2403|T-cell and B-cell Immunology"
    ]
  ],
  "openalex": "W7214754411",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754241v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/72zvrwbswrmhw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:14Z",
      "native_id": "10.64898/2026.09.24.754241",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.24.754241v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "MHC restriction is structurally encoded by the T cell receptor germline",
  "title_text": "MHC restriction is structurally encoded by the T cell receptor germline",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:14Z",
  "url": "https://research.draconitic.com/paper/72zvrwbswrmhw",
  "venue": "bioRxiv",
  "versions": []
}