2. Academic Validation
  3. Identification and characterization of dietary antigens in oral tolerance

Identification and characterization of dietary antigens in oral tolerance

  • Sci Immunol. 2026 Mar 6;11(117):eaeb4684. doi: 10.1126/sciimmunol.aeb4684.
Jamie E Blum 1 2 3,  Ryan Kong 1,  E A Schulman 2,  Francis M Chen 4,  Rabi Upadhyay 4 5,  Gabriela Romero-Meza 4 6,  Dan R Littman 4 6,  Michael A Fischbach 7 8 9 10,  Kazuki Nagashima 7 8 9 11,  Elizabeth S Sattely 1 2
Affiliations

Affiliations

  • 1 Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
  • 2 Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
  • 3 NOMIS Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • 4 Department of Cell Biology, New York University School of Medicine, New York, NY 10016, USA.
  • 5 Perlmutter Cancer Center, New York University Langone Health, New York, NY 10016, USA.
  • 6 Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.
  • 7 Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
  • 8 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
  • 9 ChEM-H Institute, Stanford University, Stanford, CA 94305, USA.
  • 10 Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • 11 Department of Molecular and Cellular Biology, Harvard University, Boston, MA 02138, USA.
PMID: 41790933 DOI: 10.1126/sciimmunol.aeb4684
Abstract

Food antigens elicit immune tolerance through the action of intestinal regulatory T (Treg) cells. Unlike food allergens, the proteins that mediate tolerance are mostly undescribed. Here, we found that epitopes derived from seed storage proteins are targets of murine intestinal Treg cells, with the most frequent response targeting the C terminus of the maize protein alpha-zein. A major histocompatibility complex (MHC) tetramer loaded with this antigen revealed that zein-specific T cells are predominantly intestinal Treg cells, develop concurrently with weaning, and constitute up to 2% of the peripheral Treg cell pool. Zein-responsive Treg cells repressed naïve T cell proliferation ex vivo, and prior dietary exposure resulted in a constrained response upon diverse inflammatory challenges in vivo, supporting a specific role for gut-resident Treg cells in suppressing systemic immune responses. Our work reveals the development, immune-suppressive characteristics, and function of naturally occurring Treg cells that recognize dietary seed storage proteins, a previously undescribed class of antigens in oral tolerance.

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