Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2003 Feb;52(2):212-7.
doi: 10.1136/gut.52.2.212.

Investigation of the putative immunodominant T cell epitopes in coeliac disease

H J Ellis  1 , E L Pollock, W Engel, J S Fraser, S Rosen-Bronson, H Wieser, P J Ciclitira
Affiliations

Investigation of the putative immunodominant T cell epitopes in coeliac disease

H J Ellis et al. Gut. 2003 Feb.

Abstract

Background: Coeliac disease (CD) is an enteropathy mediated by gluten specific T cells which secrete interferon gamma (IFN-gamma) when stimulated by gluten peptides presented by HLA-DQ2 or DQ8 molecules. Residues 62-75 of alpha(2) gliadin have been proposed as the immunodominant epitope in the majority of CD patients. Deamidation by tissue transglutaminase (tTG) of the glutamine (Q) at position 65 to glutamic acid (E) is essential for T cell stimulation.

Aims: To investigate the antigenicity of this peptide and to establish whether its T cell activating properties can be downregulated by the formation of altered peptide ligands.

Patients: Individuals with known CD.

Methods: Peptide G4 corresponding to alpha(2) gliadin residues 62-75, Q-E65 and analogues, substituting each amino acid, except E65, in turn for alanine residues, were synthesised. Small intestinal biopsies were obtained from patients. Biopsies were cultured overnight with a peptic/tryptic digest of gliadin (PTG). Lymphocytes were cultured and restimulated with tTG treated PTG. A T cell line was cloned and clones tested for stimulation and IFN-gamma production in response to G4 and its analogues.

Results: Some high activity clones were isolated with, for example, a stimulation index (SI) of 15 to G4 and secreting 327 pg/ml of IFN-gamma. Substitution of amino acids at several positions abolished or downregulated stimulation and IFN-gamma production.

Conclusions: Peptide G4 is highly immunogenic. Certain amino acid substitutions in peptide G4 abolish T cell reactivity while others are partial agonists which may have potential in immunomodulation in this condition.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Effect of alanine point substitutions of peptide G4 on stimulation of clone 4 (A) and clone 9 (B). Bars represent the mean (SEM) of triplicate counts per minute (CPM) obtained for each test. Curves shows interferon γ (IFN-γ) secretion (detection limit of the assay was 15 pg/ml in (A) and 30 pg/ml in (B)). (C) Effect of alanine point substitutions of peptide G4 on interleukin (IL)-10 and IL-4 secretion of clone 4. The lower detection limit of the IL-10 assay was 1 pg/ml and for IL-4, 1.25 pg/ml. APC, antigen presenting cells.
Figure 2
Figure 2
Proposed binding motif for peptide G4 in HLA-DQ2.6
See this image and copyright information in PMC

Comment in

References

    1. Nilsen EM, Jahnsen FL, Lundin KE, et al. Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology 1998;115:551–63. - PubMed
    1. Przemioslo RT, Lundin KE, Sollid LM, et al. Histological changes in small bowel mucosa induced by gliadin sensitive T lymphocytes can be blocked by anti-interferon gamma antibody. Gut 1995;36:874–9. - PMC - PubMed
    1. King AL, Ciclitira PJ. Celiac disease: strongly heritable, oligogenic, but genetically complex. Mol Genet Metab 2000;71:70–5. - PubMed
    1. Sollid LM. Molecular basis of celiac disease. Annu Rev Immunol 2000;18:53–81. - PubMed
    1. Anderson RP, Degano P, Godkin AJ, et al. In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope. Nat Med 2000;6:337–42. - PubMed

Publication types

MeSH terms