Celiac Disease Association with CD8+ T Cell Responses: Identification of a Novel Gliadin-Derived HLA-A2-Restricted Epitope

Abstract

One of the diagnostic hallmarks of the histological lesions associated with celiac disease is the extensive infiltration of the small intestinal epithelium by CD8+ T cells of unknown Ag specificity. In this study, we report recognition of the gliadin-derived peptide (A-gliadin 123–132) by CD8+ T lymphocytes from celiac patients. A-gliadin 123–132-specific IFN-γ production and cytotoxic activity were detected in PBMCs derived from patients on gluten-free diet, but not from either celiac patients on gluten-containing diet or healthy controls. In contrast, A-gliadin 123–132-specific cells were isolated from small intestine biopsies of patients on either gluten-free or gluten-containing diets. Short-term T cell lines derived from the small intestinal mucosa and specific for the 123–132 epitope recognized human APC pulsed with either whole recombinant α-gliadin or a partial pepsin-trypsin gliadin digest. Finally, we speculate on a possible mechanism leading to processing and presentation of class I-restricted gliadin-derived epitopes in celiac disease patients.

Multiepitope peptide-loaded virus-like particles as a vaccine against hepatitis B virus-related hepatocellular carcinoma

“…HLA-A2/K b /HBx (52-60) , HBx (92-100), HBx (115)(116)(117)(118)(119)(120)(121)(122)(123) , HBx (140)(141)(142)(143)(144)(145)(146)(147)(148) , or HBc (18)(19)(20)(21)(22)(23)(24)(25)(26)(27) complexes were synthesized and tetramerized using fusion heavy chains with ␣1 and ␣2 domains from the HLA-A2 molecule and the ␣3 domain from the H-2K b molecule as described. 19 Recombinant A2/K b and human ␤2m proteins were expressed and refolded at 4°C in the presence of each peptide.…”

“…HBc (18)(19)(20)(21)(22)(23)(24)(25)(26)(27) and the irrelevant peptide CAP-1 were evaluated as a positive and negative control, respectively, in the peptide selections. Because HLA-A*0201 is one of the most prominent HLA class I alleles, 10 HLA-A*0201-restricted HBx-derived candidate CD8 ϩ T cell epitopes (Table 1) with the highest estimated half-time of dissociation were selected, based on two epitope prediction algorithms 16,17 from HBV FMU013 strain (adw2 type, GenBank accession number: AY206384) and an epidemic strain in China.…”

“…The percentage lysis was calculated as described. 25 HLA-A*0201 blocking of CTL activity was performed by preincubating target cells with 10 g/mL anti-HLA-A2 mAb (BD Pharmingen, San Diego, CA). 24,25 The epitope specificity of tumor cell lysis was assessed in a cold target inhibition assay.…”

Identification of a β-Cell-Specific HLA Class I Restricted Epitope in Type 1 Diabetes

“…1) was analyzed using the SYF-PEITHI and BIMAS algorithms to yield nonameric peptides that might bind to HLA-A*0201 (Table 1). In our experience and those of others (13,14), scores Ն60 (BI-MAS) or Ն23 (SYFPEITHI) have the highest potential to bind to the class I heavy chain. To give consideration to the score from each ranking system with similar weighting, we used the product of these two scoring systems and then ranked the peptides according to their weighted score.…”

“…An alternate approach that is suitable for identifying epitopes in human autoimmune disease relies on predicting peptide epitopes based on the HLA type of individuals with the disease and screening the candidate peptides using mononuclear cells present in the peripheral blood of these subjects. This methodology has proven useful for predicting virus-derived HLA class I epitopes for potential use as vaccine components (11) and has also led to the identifi-cation of candidate HLA class I epitopes in other autoimmune diseases, including vitiligo (12), primary biliary cirrhosis (13), and most recently, celiac disease (14).…”