DEVELOPMENT AND CHARACTERIZATION OF DNA APTAMERS THAT TARGET GLUTEN PEPTIDES RESPONSIBLE FOR CELIAC DISEASE DEVELOPMENT
ROOPSHA BRAHMA
ROOPSHA BRAHMA
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Abstract
CELIAC DISEASE IS TRIGGERED BY EXPOSURE TO WHEAT GLUTEN AND SIMILAR PROTEINS FOUND IN BARLEY AND RYE. WE SELECTED TWO SETS OF SINGLE STRAND DNA APTAMERS THAT TARGET THE IMMUNODOMINANT 33-MER GLUTEN EPITOPE AND INVESTIGATED THEIR ABILITY TO PREVENT GLUTEN-INDUCED AUTOIMMUNITY. THE FIRST SET OF APTAMERS, WHICH BIND TO THE NATIVE 33-MER GLUTEN PEPTIDE (LQLQPFPQPQLPYPQPQPLYPQPQLPYPQPQPF), INHIBITS TISSUE TRANSGLUTAMINASE-MEDIATED DEAMIDATION WHICH IS A NECESSARY STEP IN CELIAC DISEASE DEVELOPMENT. THE SECOND SET OF APTAMERS, WHICH BIND TO THE DEAMIDATED 33-MER GLUTEN PEPTIDE (LQLQPFPQPELPYPQPEPLYPQPELPYPQPQPF), HINDERS EPITOPE LOADING ONTO HLA-DQ2. THESE APTAMERS MAY SERVE AS A PREVENTIVE THERAPEUTIC FOR CELIAC DISEASE.
Keywords
Aptamer, Celiac disease, autoimmune disorder, tissue transglutaminase, DQ2
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Date
2013-08-22
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Thesis