Single-chain recombinant HLA-DQ2.5/peptide molecules block α2-gliadin-specific pathogenic CD4 T-cell proliferation and attenuate production of inflammatory cytokines: A potential therapy for celiac disease

J. Huan, R. Meza-Romero, J. L. Mooney, A. A. Vandenbark, H. Offner, G. G. Burrows

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Celiac disease (CD) is a disorder of the small intestine caused by intolerance to wheat gluten and related proteins in barley and rye. CD4 T cells have a central role in CD, recognizing and binding complexes of HLA-DQ2.5 bearing gluten peptides that have survived digestion and that are deamidated by tissue transglutaminase (TG2), propagating a cascade of inflammatory processes that damage and eventually destroy the villous tissue structures of the small intestine. In this study, we present data showing that recombinant DQ2.5-derived molecules bearing covalently tethered α2-gliadin-61-71 peptide have a remarkable ability to block antigen-specific T-cell proliferation and inhibited proinflammatory cytokine secretion in human DQ2.5-restricted α2-gliadin-specific T-cell clones obtained from patients with CD. The results from our in vitro studies suggest that HLA-DQ2.5-derived molecules could significantly inhibit and perhaps reverse the intestinal pathology caused by T-cell-mediated inflammation and the associated production of proinflammatory cytokines.

Original languageEnglish (US)
Pages (from-to)112-120
Number of pages9
JournalMucosal Immunology
Volume4
Issue number1
DOIs
StatePublished - Jan 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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