{
  "template": "magazine",
  "title": "One Antigen, Two Diseases: Shared pMHC Biology Across EoE and Celiac Disease",
  "subtitle": "Food-antigen presentation on MHC-I/II converges across esophagus and gut, nominating shared diagnostics and gut-restricted biologics.",
  "authors": "EoE \u00d7 Celiac pMHC Working Group",
  "affiliation": "Built with Claude \u00b7 Life Sciences Hackathon 2025",
  "palette": "editorial_teal",
  "width_in": 56,
  "height_in": 31.5,
  "columns": 4,
  "gutter_in": 0.55,
  "body_pt": 24,
  "max_img_h_in": 3.4,
  "title_h_in": 3.0,
  "stats_h_in": 1.9,
  "footer_h_in": 1.7,
  "stats": [
    {
      "value": "2",
      "label": "diseases \u00b7 one pMHC pipeline"
    },
    {
      "value": "2,287",
      "label": "strong MHC-II binders \u00b7 5 DRB1 alleles"
    },
    {
      "value": "925",
      "label": "strong on HLA-DRB1*01:01 (38% of 2,428)"
    },
    {
      "value": "\u221249%",
      "label": "protease sites in hardened binders"
    },
    {
      "value": "20",
      "label": "antibody-tractable EoE targets"
    }
  ],
  "qr_url": "https://example.org/eoe-celiac-pmhc",
  "footer_text": "Data: internal EoE/celiac pMHC streams \u00b7 netMHCpan / netMHCIIpan (IEDB) \u00b7 contact: pmhc-working-group@example.org",
  "sections": [
    {
      "title": "Background & Rationale",
      "body": "EoE: food-antigen-driven Th2 esophageal disease\nCeliac: HLA-DQ-restricted, gluten-driven small-bowel disease\nBoth hinge on antigen presentation, not cytokines alone\nElemental diet \u2192 remission in >90% of EoE children",
      "column": 0
    },
    {
      "title": "The Shared-Antigen Hypothesis",
      "body": "Same food proteins cross the barrier in both diseases\nMilk Bos d 5 & egg Gal d 1 presented in BOTH panels\nOne pMHC pipeline + shared antigens \u2192 transferable targets\nCeliac's mapped epitopes = ground truth for the EoE pipeline",
      "callout": "One pipeline, two diseases \u2192 transferable targets",
      "column": 1
    },
    {
      "title": "Methods / Pipeline",
      "body": "Disease-agnostic: antigens \u2192 UniProt \u2192 HLA binding \u2192 burden\nClass II: netMHCIIpan (IEDB); class I: netMHCpan-class\nCeliac adds TG2 deamidation (native vs deamidated 15-mers)\nBenchmarked vs 31 known celiac epitopes; 13-allele cross-check",
      "column": 2
    },
    {
      "title": "pMHC-II Risk-Allele Landscape",
      "body": "2,428 peptide predictions per allele across 5 DRB1 risk alleles\nStrong = standard netMHCIIpan cutoff; 2,287 strong total\nHLA-DRB1*01:01 dominates: 925 strong (38.1%), best 4.26 nM\n*07:01 445 \u00b7 *15:01 420 \u00b7 *04:01 390 \u00b7 *03:01 107",
      "image": "figB_alleles.png",
      "caption": "Strong MHC-II binders per DRB1 allele (of 2,428 predictions each).",
      "callout": "Use rank & allele-preference, not absolute IC50, for DQ/DR calls",
      "column": 3
    },
    {
      "title": "pMHC-I Landscape (Secondary Axis)",
      "body": "372 peptides screened; only 9 strong (\u226450 nM) \u2014 sparse axis\nAcross all 372, top HLA-I restrictions: A*02:01, B*08:01, A*03:01\nMatches IFN-\u03b3-driven epithelial HLA-I induction\nExploratory sub-study, secondary to the CD4/Th2 class-II arm",
      "column": 0
    },
    {
      "title": "Shared Food-Antigen Load: EoE vs Celiac",
      "body": "Milk Bos d 5 (178 aa): 28 MHC-I + 212 MHC-II strong\n= 15.7 (I) and 119.1 (II) strong binders per 100 aa\nEgg Gal d 1 (210 aa): 13 MHC-I + 91 MHC-II strong\nClass II \u226b class I \u2192 one shared-antigen reagent set",
      "image": "figA_dualload.png",
      "caption": "Strong binders per 100 aa (netMHCpan/netMHCIIpan). Class II \u226b class I.",
      "column": 2
    },
    {
      "title": "EoE Target Shortlist",
      "body": "20 candidate genes, all antibody-tractable\nTop effect: POSTN 5.55 \u00b7 CDH26 4.98 \u00b7 ANO1 3.91 (log2FC)\nAlso NTRK2 3.13 \u00b7 MSLN 3.00\nEffector/receptor targets downstream of presentation",
      "column": 1
    },
    {
      "title": "Gut-Restricted Binder Engineering",
      "body": "mica_decoy: protease-labile sites \u221245.5% (123\u219267)\ntrypsin sites 32\u21925; net charge \u221210\u2192\u221242\nil15_binder: sites \u221249.4% (85\u219243); trypsin 18\u21921\nStructural cysteines retained \u2192 survives gut proteases",
      "image": "figD_hardening.png",
      "caption": "Protease-labile sites before/after hardening.",
      "column": 3
    },
    {
      "title": "Diagnostic Peptide Pools",
      "body": "Milk 720 epitopes / 6 proteins \u2014 largest pool\nSoy 526/2 \u00b7 Wheat 204/1\nFish 49 \u00b7 Egg 39 \u00b7 Peanut 39 \u00b7 Tree nut 37 \u00b7 Shellfish 12\nPer-patient HLA-guided pools focus T-cell assays",
      "image": "figC_pools.png",
      "caption": "Strong epitopes per food pool; milk & soy dominate.",
      "column": 0
    },
    {
      "title": "Conclusions & Next Steps",
      "body": "\u2022 Shared milk/egg antigens jointly presented (MHC-I & II) in EoE + celiac; class II dominates\n\u2022 DRB1*01:01 & DQ2.5 anchor risk; per-patient panels beat allele gating\n\u2022 Hardened binders cut protease sites 45\u201349%, keep structural Cys\n\u2022 Next: shared peptide-pool platform; validate top DQ2.5/DRB1 hits (AIM/tetramer); pair with POSTN/CDH26/ANO1",
      "accent": "accent2",
      "column": 1
    }
  ],
  "speaker_notes": "[Background] EoE and celiac are both antigen-driven diseases where food proteins cross a defective barrier and get presented via MHC to T cells -- EoE via CD4/Th2, celiac via HLA-DQ-restricted gluten response. [Hypothesis] We tested whether a single pMHC pipeline, run across both diseases, finds shared food antigens and transferable design lessons. [Methods] Same antigen-to-panel pipeline, with celiac adding a TG2-deamidation step and a unique benchmark against 31 known Sollid epitopes. [Landscape] Class II dominates: DRB1*01:01 carries 925 of 1800 strong binder predictions; class I is sparse (9/372 strong) and secondary. [Shared load] Milk and egg antigens are jointly presented in both diseases, with class-II binder density around 10x class-I. [Engineering] Protease-hardening cut cleavage sites by 45-49% in two candidate binders, aimed at gut-stable reagents. [Diagnostics] Milk and soy dominate the diagnostic peptide-pool sizes (720 and 526 strong epitopes). [Ask] We're seeking collaborators for functional validation (tetramer/AIM assays) of top-ranked DQ2.5/DRB1 peptides and feedback on the shared-antigen diagnostic pool design."
}