{
  "abstract": "Rapid advances in protein design enable new approaches in adoptive cell therapy, but foreign proteins can elicit cytotoxic T cell responses, and hence there is considerable need for approaches which reduce immunogenicity without compromising protein function. Here, we develop a computational framework integrating structure-guided sequence design with MHC class I epitope prediction to efficiently tune protein immunogenicity while preserving function. Using a de novo-designed luciferase as a model, we demonstrate epitope elimination while preserving function across 5 common mouse alleles and extend our computational optimization to 25 common human MHC-I alleles. In mice immunized with mRNA-lipid nanoparticles, variants designed to have few MHC-I epitopes elicited little detectable CD8 T cell response, whereas variants designed to include multiple epitopes induced robust responses. Together, these results demonstrate that the CD8 T cell immunogenicity of designed proteins can be tuned while preserving function, opening the door to incorporation of designed proteins in a next generation of adoptive cell therapies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.",
    "Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.",
    "Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.",
    "Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, 9 Denmark",
    "Massachusetts General Hospital Cancer Center, Boston, MA 02129, USA.",
    "Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA."
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Bingxu Liu",
      "orcid": "0000-0002-3661-3410"
    },
    {
      "affs": [
        2
      ],
      "name": "Tianyang Mao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Max H Witwer"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Oliver Morell"
    },
    {
      "affs": [
        2,
        4
      ],
      "name": "Nir Hacohen"
    },
    {
      "affs": [
        0,
        1,
        5
      ],
      "name": "David Baker"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bj9d5g4zs0vbq.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.24.761497",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761497v1.full",
  "id": "bj9d5g4zs0vbq",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761497v1",
  "language": "en",
  "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",
      "bioengineering"
    ],
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1312|vaccines and immunoinformatics approaches"
    ]
  ],
  "openalex": "W7223973668",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761497v1.full.pdf",
  "pmcid": "PMC13733841",
  "pmid": "42990359",
  "published": "2026-10-24",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/bj9d5g4zs0vbq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:47Z",
      "native_id": "10.64898/2026.10.24.761497",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.24.761497v1"
    },
    {
      "first_seen": "2026-11-08T12:23:32Z",
      "native_id": "PMC13733841",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.24.761497"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioengineering",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Function-preserving CD8⁺ T Cell Immunogenicity minimization through protein design",
  "title_text": "Function-preserving CD8⁺ T Cell Immunogenicity minimization through protein design",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:32Z",
  "url": "https://research.draconitic.com/paper/bj9d5g4zs0vbq",
  "venue": "bioRxiv",
  "versions": []
}