{
  "abstract": "Background: Mycobacterium tuberculosis (Mtb) remains a primary global health challenge, particularly in HIV-co-infected populations where viral Nef-mediated downregulation of classical MHC-I molecules impairs T-cell immunity. Conversely, the non-classical MHC-Ib molecule, HLA-E, is resistant to Nef-mediated evasion, representing an attractive, non-polymorphic pathway for investigating potential Mtb-specific CD8+ T-cell activation targets.\n\nMethods: This study utilized an exploratory in vitro screening and in silico modeling framework to identify candidate HLA-E-binding Mtb peptides. Candidate ligands were screened by biopanning an Mtb F15/LAM4/KZN phage secretome library against immobilized recombinant HLA-E*01:03. Identified peptides were characterized via DNA sequencing, and their predicted structural–mechanical interactions were evaluated using molecular docking and normal mode analysis (NMA).\n\nResults: Phage selection yielded distinct Mtb-derived peptide fragments, including components from known immunogenic antigens Rv1980c (Mpt64) and Rv2875 (Mpt70), alongside conserved hypothetical proteins such as Rv1566c. Structural profiling predicted groove-directed anchoring within the modeled HLA-E binding cleft, displaying a spatial preference for pockets E and F. Computational molecular scoring prioritized favorable candidates (e.g., Rv2972c at −87.49 kcal/mol), while NMA indicated that these prioritized Mtb peptides possess a higher degree of predicted conformational plasticity (eigenvalues as low as 9.13 × 10-6) compared to the rigid Mtb44 baseline (1.37 × 10–4).\n\nConclusion: These findings map an exploratory Mtb peptide repertoire demonstrating computational feasibility for flexible HLA-E groove accommodation. By providing a structural foundation for candidate peptide prioritization, these results lay the groundwork for future investigations into unconventional CD8+ T-cell activation and the rational design of next-generation TB vaccines tailored for high-burden TB/HIV co-infection settings.",
  "abstract_shown": true,
  "affiliations": [
    "School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa",
    "Discipline of Microbiology, School of Agriculture and Science, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa",
    "Igagasi Biotech (Pty) Ltd, TIA Bioprocessing Platform, Durban, KwaZulu-Natal, South Africa"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nkanyezi Masondo"
    },
    {
      "affs": [
        0
      ],
      "name": "Michelle Lucille Gordon"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Thamsanqa Emmanuel Chiliza"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/16d2469k7vxr7.bib",
  "cited_by": 0,
  "doi": "10.3389/fcimb.2026.1724374",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13730909/",
  "id": "16d2469k7vxr7",
  "issns": [
    "2235-2988"
  ],
  "landing_url": "https://doi.org/10.3389/fcimb.2026.1724374",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1312|vaccines and immunoinformatics approaches"
    ]
  ],
  "openalex": "W7223145761",
  "pdf_url": "https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2026.1724374/pdf",
  "pmcid": "PMC13730909",
  "pmid": "42984503",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/16d2469k7vxr7.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:23:52Z",
      "native_id": "PMC13730909",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fcimb.2026.1724374"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|vaccines and immunoinformatics approaches",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Identification of candidate HLA-E binding peptides from Mycobacterium tuberculosis using phage secretome library screening and computational modeling",
  "title_text": "Identification of candidate HLA-E binding peptides from Mycobacterium tuberculosis using phage secretome library screening and computational modeling",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:12Z",
  "url": "https://research.draconitic.com/paper/16d2469k7vxr7",
  "venue": "Frontiers in Cellular and Infection Microbiology",
  "versions": []
}