Antigen presentation to celiac lesion-derived T cells of a 33-mer gliadin peptide naturally formed by gastrointestinal digestion.

Abstract

Celiac disease is an HLA-DQ2-associated disorder characterized by intestinal T cell responses to ingested wheat gluten proteins. A peptide fragment of 33 residues (alpha(2)-gliadin 56-88) produced by normal gastrointestinal proteolysis contains six partly overlapping copies of three T cell epitopes and is a remarkably potent T cell stimulator after deamidation by tissue transglutaminase (TG2). This 33-mer is rich in proline residues and adopts the type II polyproline helical conformation in solution. In this study we report that after deamidation, the 33-mer bound with higher affinity to DQ2 compared with other monovalent peptides harboring gliadin epitopes. We found that the TG2-treated 33-mer was presented equally effectively by live and glutaraldehyde-fixed, EBV-transformed B cells. The TG2-treated 33-mer was also effectively presented by glutaraldehyde-fixed dendritic cells, albeit live dendritic cells were the most effective APCs. A strikingly increased T cell stimulatory potency of the 33-mer compared with a 12-mer peptide was also seen with fixed APCs. The 33-mer showed binding maximum to DQ2 at pH 6.3, higher than maxima found for other high affinity DQ2 binders. The 33-mer is thus a potent T cell stimulator that does not require further processing within APC for T cell presentation and that binds to DQ2 with a pH profile that promotes extracellular binding.

• Authors: Shuo-Wang Qiao, Elin Bergseng, Øyvind Molberg, Jiang Xia, Burkhard Fleckenstein, Chaitan Khosla, Ludvig M Sollid
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 173 Issue 3 Pg. 1757-62 (Aug 01 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15265905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Epitopes
• Fixatives
• HLA-DQ Antigens
• HLA-DQ2 antigen
• Peptide Fragments
• Recombinant Proteins
• alpha2-gliadin (56-88)
• Gliadin
• Proline
• Protein Glutamine gamma Glutamyltransferase 2
• Transglutaminases
• GTP-Binding Proteins
• Glutaral

Topics

• Amino Acid Sequence
• Antigen Presentation
• B-Lymphocytes (drug effects, immunology)
• Celiac Disease (immunology, pathology)
• Cell Line, Transformed
• Dendritic Cells (drug effects, immunology)
• Digestion
• Epitopes (immunology)
• Fixatives (pharmacology)
• GTP-Binding Proteins (metabolism)
• Gliadin (chemistry, immunology, metabolism)
• Glutaral (pharmacology)
• HLA-DQ Antigens (immunology)
• Herpesvirus 4, Human
• Hydrogen-Ion Concentration
• Molecular Sequence Data
• Peptide Fragments (chemistry, immunology)
• Proline (chemistry)
• Protein Binding
• Protein Glutamine gamma Glutamyltransferase 2
• Protein Structure, Secondary
• Recombinant Proteins (metabolism)
• T-Lymphocyte Subsets (immunology)
• Transglutaminases (metabolism)