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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Peripheral T cell response to A-gliadin in celiac disease: differential processing and presentation capacities of Epstein-Barr-transformed B cells and fibroblasts.

Celiac disease ( CD) is a small intestinal disorder characterized by the malabsorption of most nutrients. Disease pathogenesis appears to be associated with immune-mediated pathology. Susceptibility is associated with genes coding for DQw2 class II molecules. In the present report we investigated T cell responses to A-gliadin ( AGL), a major alpha-gliadin component known to activate disease. Gliadin-specific lines were generated from a CD patient and a normal donor. Three major points were revealed by the analysis of these T cells: (1) On the basis of mapping experiments using Epstein-Barr virus (EBV) lines and DR-transfected fibroblasts and DR-, DP-, and DQ-specific monoclonal antibodies (mAb), all responses appeared to be DR-restricted. Thus, in contrast to the strong association of disease susceptibility with DQ molecules, no DQ-restricted, gliadin-specific response was detectable. (2) Fine specificity analysis, using a panel of synthetic peptides spanning the entire alpha-gliadin component molecule, revealed that the clones derived from the normal donor were DR53-restricted and AGL 21-40-specific, while clones derived from the CD patient were DR7-restricted and peptide 1-20-specific. (3) Both whole AGL and AGL 1-20 were presented to the patient-derived clones with much higher efficiency by DDR-transfected fibroblasts than by EBV lines. These data suggested that fibroblasts processed this determinant efficiently, while EBV lines were unable to do so. Indeed, analysis of a panel of truncated AGL 1-20 analogs revealed that peptide AGL 1-8, which contained the minimal T cell epitope, was presented with equal efficiency by fixed or irradiated EBV and irradiated DR7-transfected fibroblasts.[1]

References

  1. Peripheral T cell response to A-gliadin in celiac disease: differential processing and presentation capacities of Epstein-Barr-transformed B cells and fibroblasts. Franco, A., Appella, E., Kagnoff, M.F., Chowers, Y., Sakaguchi, K., Grey, H.M., Sette, A. Clin. Immunol. Immunopathol. (1994) [Pubmed]
 
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