In vitro activities of A-gliadin-related synthetic peptides: damaging effect on the atrophic coeliac mucosa and activation of mucosal immune response in the treated coeliac mucosa

Scand J Gastroenterol. 1996 Mar;31(3):247-53. doi: 10.3109/00365529609004874.

Abstract

Background: Gliadin amino acid sequence(s) responsible for toxicity in susceptible individuals have not been fully elucidated. Previous in vitro studies have suggested the presence of active sequences in the NH(2)-terminal part of the A-gliadin molecule. In this paper the in vitro activity of A-gliadin synthetic peptides 31-55, 31-43, and 44-55 has been investigated.

Methods: Organ culture of jejunal mucosa from untreated and treated coeliac patients was used. In the first system enterocyte height was used as a measure of peptide toxicity; in the second system evidence of activated mucosal cell-mediated immune response was sought.

Results: Peptides 31-55 and 31-43 were active on untreated coeliac mucosa at a concentration of 0.5 mg/ml and peptide 44-55 only at a concentration of 3 mg/ml. In in vitro-cultured treated coeliac mucosa peptides 31-55 and 31-43 at 1 mg/ml and peptide 44-55 at 3 mg/ml were able to induce enhanced epithelial expression of HLA-DR and 4F2 molecules and the appearance of CD25 positive cells.

Conclusions: Our results suggest that 31-43 and 44-55 A-gliadin peptides are both active, even if to different extents. In vitro systems remain essential tools to screen material to be subsequently tested in vivo.

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / metabolism
  • Carrier Proteins / metabolism
  • Celiac Disease / diet therapy
  • Celiac Disease / immunology
  • Celiac Disease / pathology*
  • Child
  • Epitopes / immunology
  • Fusion Regulatory Protein-1
  • Gliadin / chemical synthesis
  • Gliadin / immunology
  • Gliadin / pharmacology*
  • HLA-DR Antigens / metabolism
  • Humans
  • Immunity, Cellular
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology*
  • Jejunum / immunology
  • Jejunum / metabolism
  • Organ Culture Techniques
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / pharmacology*
  • Receptors, Interleukin-2 / analysis

Substances

  • Antigens, CD
  • Carrier Proteins
  • Epitopes
  • Fusion Regulatory Protein-1
  • HLA-DR Antigens
  • Peptide Fragments
  • Receptors, Interleukin-2
  • Gliadin