EoE pMHC-II Therapeutics: 3D Interactive Viewer

Biotech Pitch Tool: Rotate, zoom, and inspect the three food-allergen pMHC-II structures (dairy, wheat, soy) designed for tolerance induction. Each structure shows the canonical peptide positioning in the HLA-II binding groove, with color-coded epitopes and HLA chains.

1. Epitope Structures & Canonical Positioning

All three food-allergen epitopes achieve canonical positioning in the HLA-DRB1*07:01 binding groove (15/15 peptide residues, 59–64 buried contacts of 90 total MHC-peptide contacts). Color coding:

Dairy Epitope (FAQTQSLVY)

Dairy (Precursor, aa59–78)
IC50: 16.78 nM | Rank: 0.94
ipTM: 0.872 | pLDDT: 0.859

Wheat Epitope (HNVVHAIIL)

Wheat (Reframed, cysteine-free)
IC50: 35.01 nM | Rank: 0.49
ipTM: 0.896 | pLDDT: 0.884

Soy Epitope (FVVNATSNL)

Soy (Gly m 6)
IC50: 50.31 nM | Rank: 0.76
ipTM: 0.891 | pLDDT: 0.878

2. Epitope Comparison Table

3. Nanoparticle Platform Architecture

Epitope	Sequence	IC50 (nM)	Rank %ile	ipTM	pLDDT	Status
Dairy	FAQTQSLVY	16.78	0.94	0.872	0.859	✓ Publication-Ready
Wheat	HNVVHAIIL	35.01	0.49	0.896	0.884	Phase 1 Validation
Soy	FVVNATSNL	50.31	0.76	0.891	0.878	Phase 1 Validation

Multivalent pMHC-II Display:

Core: 20 nm Fe₃O₄ (iron oxide)
Surface coating: ~75 PEG₂ₖ-maleimide linkers (2 nm spacing)
pMHC copies: 5 per nanoparticle
Inter-epitope spacing: 5.8 nm (optimal for TCR clustering)
Surface occupancy: 1.4% (low crowding, high accessibility)
Avidity gain: ~24-fold (5-fold multivalency)

Regulatory T Cell (Tr1) Induction Mechanism: Multivalent platform engages multiple TCRs simultaneously, promoting CD39+CD73+ IL-10-producing Tr1 differentiation. Avidity enhancement compensates for any affinity loss from epitope engineering (e.g., wheat cysteine reframing).

4. TCR Engagement & Tr1 Activation

Dairy pMHC + TCR Complex (Docked)

TCR recognition of dairy epitope
Shows canonical TCR positioning and contacts with pMHC-II groove.

5. Biotech Development Roadmap

Phase	Timeline	Budget	Key Deliverables
Phase 1	Weeks 1–14	$40–65k	Human ex vivo CD4+ IL-10 validation; Phase 1b in vivo proof-of-mechanism (n=5–10)
Phase 2	Weeks 15–26	$35–55k	BALB/c EoE model efficacy (≥40% eosinophil reduction vs. placebo)
Phase 3	Weeks 27–42	$105–170k	GLP toxicology (28d acute) + 6-month extended biodegradation
Phase 4	Weeks 43–72	$80–140k	GMP manufacturing scale-up & process validation (≥50% yield)
Phase 5	Weeks 73–84	$15–27k	IND dossier assembly & FDA Pre-IND meeting
TOTAL	18–24 months	$275–457k	IND submission (month 18–20)

6. Critical Regulatory Pathway

Multi-HLA Expansion (Weeks 1–4, Parallel to Phase 1):

Current design is HLA-DRB1*07:01 restricted (~30–35% of North American EoE patients). Immediate IEDB mapping for DQ2, DQ8, DQ5, DR4 alleles will expand population coverage to ≥70%, enabling Phase 2 IND breakthrough designation and stronger biotech licensing.

Built with Claude Science | July 2026
Authored by Ruth-Anne Pai, PhD (EoE patient-researcher) | Biohub-supported hackathon project

EoE pMHC-II Nanoparticle Therapeutics: 3D Interactive Viewer