{
  "abstract": "HLA class I antigen presentation depends on coordinated peptide processing, transport and loading, yet inflammatory signalling may modify the consequences of defects in this machinery. We examined wild-type HAP1 cells and isogenic ERAP1-, TAP1- and TAP2-knockout cells before and after interferon-γ (IFNγ) treatment using flow cytometry, proteomics, and immunopeptidomics. IFNγ strongly induced residual antigen-processing machinery in all HAP1-genotypes, increased HLA-I surface expression and expanded peptide recovery, including peptides derived from cancer-associated antigens. However, repertoire restoration was incomplete and defect-specific. ERAP1-deficient cells retained enrichment of longer, terminally extended peptides, whereas TAP2-deficient cells retained alterations in peptide length, processing of peptide flanking regions and source-protein location of the peptide. TAP1-deficient cells showed the greatest convergence to wards wild-type immunopeptidome features upon IFNγ stimulation. Components of the peptide-loading and ER quality-control machinery remained associated with immature HLA-I heavy chains in TAP-deficient cells and were enhanced by exposure to IFNγ. These findings demonstrate that inflammatory signalling can quantitatively and partially qualitatively compensate for defects in HLA-I antigen processing by amplifying intact pathway components and alternative peptide supply, without recreating a fully wild-type immunopeptidome.",
  "abstract_shown": true,
  "affiliations": [
    "Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia",
    "Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, VIC 3800, Australia"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Ritchlynn Aranha"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mohadeseh Dastpeyman"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kirti Pandey",
      "orcid": "0000-0003-0799-6376"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mohammadreza Dorvash"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rochelle Ayala",
      "orcid": "0000-0001-8538-8857"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Nathan P. Croft",
      "orcid": "0000-0002-2128-5127"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Anthony W. Purcell",
      "orcid": "0000-0003-0532-8331"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/13dhsaqdyfgvs.bib",
  "cited_by": 0,
  "doi": "10.3390/cells15201914",
  "fulltext_url": "https://europepmc.org/articles/PMC13703434",
  "id": "13dhsaqdyfgvs",
  "issns": [
    "2073-4409"
  ],
  "landing_url": "https://www.mdpi.com/2073-4409/15/20/1914",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2403|Immunotherapy and Immune Responses"
    ]
  ],
  "openalex": "W7207526934",
  "pdf_url": "https://europepmc.org/articles/PMC13703434?pdf=render",
  "pmcid": "PMC13703434",
  "pmid": "42929886",
  "published": "2026-10-21",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/13dhsaqdyfgvs.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:02Z",
      "native_id": "10.3390/cells15201914",
      "source": "crossref",
      "url": "https://www.mdpi.com/2073-4409/15/20/1914"
    },
    {
      "first_seen": "2026-10-30T12:22:01Z",
      "native_id": "MED:42929886",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42929886"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Immunotherapy and Immune Responses",
      "subfield": "immunology"
    }
  ],
  "title": "Cytokine-Mediated Plasticity in the Molecular Requirements for Peptide-Loading Complex Formation and Antigen Presentation",
  "title_text": "Cytokine-Mediated Plasticity in the Molecular Requirements for Peptide-Loading Complex Formation and Antigen Presentation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:22:01Z",
  "url": "https://research.draconitic.com/paper/13dhsaqdyfgvs",
  "venue": "Cells",
  "versions": []
}