Epitopes described in "Induction of antigen-specific tolerance by oral administration of Lactococcus lactis delivered immunodominant DQ8-restricted gliadin peptide in sensitized nonobese diabetic Abo Dq8 transgenic mice."

Reference
Article Authors:Inge L Huibregtse; Eric V Marietta; Shadi Rashtak; Frits Koning; Pieter Rottiers; Chella S David; Sander J H van Deventer; Joseph A Murray
Article Title:Induction of antigen-specific tolerance by oral administration of Lactococcus lactis delivered immunodominant DQ8-restricted gliadin peptide in sensitized nonobese diabetic Abo Dq8 transgenic mice.
Reference Detail
Reference ID:1016351
Abstract:Active delivery of recombinant autoantigens or allergens at the intestinal mucosa by genetically modified Lactococcus lactis (LL) provides a novel therapeutic approach for the induction of tolerance. Celiac disease is associated with either HLA-DQ2- or HLA-DQ8-restricted responses to specific antigenic epitopes of gliadin, and may be treated by induction of Ag-specific tolerance. We investigated whether oral administration of LL-delivered DQ8-specific gliadin epitope induces Ag-specific tolerance. LL was engineered to secrete a deamidated DQ8 gliadin epitope (LL-eDQ8d) and the induction of Ag-specific tolerance was studied in NOD AB degrees DQ8 transgenic mice. Tolerance was assessed by delayed-type hypersensitivity reaction, cytokine measurements, eDQ8d-specific proliferation, and regulatory T cell analysis. Oral administration of LL-eDQ8d induced suppression of local and systemic DQ8-restricted T cell responses in NOD AB degrees DQ8 transgenic mice. Treatment resulted in an Ag-specific decrease of the proliferative capacity of inguinal lymph node (ILN) cells and lamina propria cells. Production of IL-10 and TGF-beta and a significant induction of Foxp3(+) regulatory T cells were associated with the eDQ8d-specific suppression induced by LL-eDQ8d. These data provide support for the development of effective therapeutic approaches for gluten-sensitive disorders using orally administered Ag-secreting LL. Such treatments may be effective even in the setting of established hypersensitivity.
Date:2009
Reference Type:Literature
PubMed ID:19635921
Journal:J Immunol
Journal Volume:183
Article Pages:2390-6
Journal ISSN:0022-1767
Article Chemical List:Epitopes, T-Lymphocyte;HLA-DQ Antigens;HLA-DQ8 antigen;Immunodominant Epitopes;Peptide Fragments;Gliadin
Article MeSH List:Administration, Oral; Amino Acid Sequence; Animals; Base Sequence; Celiac Disease(immunology; microbiology; therapy); Clone Cells; Disease Models, Animal; Epitopes, T-Lymphocyte(administration & dosage; genetics; immunology); Gliadin(administration & dosage; genetics; immunology); HLA-DQ Antigens(genetics; immunology); Humans; Immune Tolerance(genetics); Immunization; Immunodominant Epitopes(administration & dosage; genetics; immunology); Intestinal Mucosa(immunology; microbiology; pathology); Lactococcus lactis(genetics; immunology); Mice; Mice, Inbred NOD; Mice, Transgenic; Molecular Sequence Data; Peptide Fragments(administration & dosage; genetics; immunology)
Curation Last Updated:2014-07-16 22:15:22