ACTIVATION OF CELIAC-DISEASE IMMUNE-SYSTEM BY SPECIFIC ALPHA-GLIADIN PEPTIDES

Two different gliadin molecules (designated alpha-gliadin and alpha/be ta-gliadin) were synthesized as 52 and 58 ten amino acid (aa) long ove rlapping peptides for the determination of their B-cell epitopes. Mono clonal antibodies and human serum pools revealed two epitopes common f or both gliadins (peptide 14 aa:s 66-75 and peptides 34 alpha aa:s 166 -175, 36 alpha/beta aa:s 176-185) and two unique epitopes (alpha-gliad in peptides 48 aa:s 236-245 and alpha/beta-gliadin peptide 52 aa:s 256 -275). In addition, peptide 9 (QPYPQPQPFP) aa:s 41-50 and peptide 42 ( LGQGSFRPSQ) aa:s 206-215 were detectable by monoclonal antibodies and serum pools from patients with untreated celiac disease but not by ser um pools from disease control patients who had antigliadin antibodies. Patients with celiac disease were also studied for their human leukoc yte antigen (HLA) class II status (the presence of genetically determi ned proteins on antigen-presenting cells that are important for immuno logical recognition). Antigliadin antibody response to peptide QPYPQPQ PFP was restricted by celiac disease (and HLA class II) because relati ve amounts of the antipeptide antibodies were significantly (P < 0.05) increased in celiac disease patients. The HLA alleles DQA10501 and D QB10201 are strongly associated with celiac disease. The difference b etween patients with celiac disease and healthy control subjects with regard to peptide QPYPQPQPFP suggest that this region in the gliadin m olecule is of pathogenetic importance in celiac disease.