{
  "abstract": "Identifying antibody features that reliably encode epitope specificity poses a major barrier towards modeling antigen-antibody interactions. Affinity maturation offers a unique opportunity to probe the molecular basis of antigen-antibody interactions by revealing how individual somatic hypermutations (SHM) refine antibody binding. Using SARS-CoV-2 spike-specific germinal center B-cell repertoires, we show that antibodies harboring multiple SHMs that are restricted to their respective clonotypes (clonotype-restricted SHMs) preferentially recognize cryptic epitopes. We structurally characterized three such antibodies: two recognized a cryptic epitope on the receptor-binding domain whereas a third bound an N-terminal domain epitope that is almost entirely occluded in prefusion spike. In contrast, SHMs shared across multiple clonotypes using the same V gene recur across antibodies targeting diverse antigens but generally fail to enhance affinity when introduced into diverse antibody backgrounds. Together, these findings define a spectrum of SHM behavior, distinguishing epitope-tailored mutations from broadly recurrent but largely permissive substitutions.",
  "abstract_shown": true,
  "affiliations": [
    "Icahn School of Medicine at Mount Sinai"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "V. N. Rao"
    },
    {
      "name": "B. Bonnettaz"
    },
    {
      "name": "A. Civljak"
    },
    {
      "name": "A. Abbad"
    },
    {
      "name": "F. Krammer"
    },
    {
      "name": "C. H. Coelho"
    },
    {
      "affs": [
        0
      ],
      "name": "G. Bajic"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/btp8x565363yy.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.10.758199",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758199v1.full",
  "id": "btp8x565363yy",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758199v1",
  "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",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7222826339",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758199v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/btp8x565363yy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:15Z",
      "native_id": "10.64898/2026.10.10.758199",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.10.758199v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Clonotype specificity distinguishes epitope-tailored and permissive somatic hypermutation",
  "title_text": "Clonotype specificity distinguishes epitope-tailored and permissive somatic hypermutation",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:15Z",
  "url": "https://research.draconitic.com/paper/btp8x565363yy",
  "venue": "bioRxiv",
  "versions": []
}