Oral tolerance is the mechanism by which the immune system remains unresponsive to orally administered soluble antigens. @entity19 immunized with @entity1 TG (hTG), resulting in the induction of experimental @entity1669 (EAT), provide an ideal in vivo system in which to examine oral tolerance to hTG. In the present study, we characterize epitopes of hTG that are capable of inducing oral tolerance. hTG is a large homodimeric protein, 660 Kd. The limited proteolysis of hTG using trypsin (TR) generates several smaller fragments of hTG ranging in size from 29 Kd to 145 Kd. Using hTG fragments h1TR (residues 1-521), h4bisTR (residues 2513-2713), h6TR (residues 522-1626), and h7TR (residues 1627-2512), prepared from both @entity1496 rich and @entity1496 poor hTG, we investigated the ability of these fragments to induce oral tolerance. The oral administration of @entity1496 rich h6TR or h7TR suppresses hTG specific immune responses in a manner similar to whole hTG. In contrast, the oral administration of @entity1496 rich h1TR or h4bisTR exacerbates hTG specific immune responses. Unlike @entity1496 rich h1TR or h4bisTR, the oral administration of @entity1496 poor h1TR or h4bisTR fails to augment hTG specific immune responses. In fact, h4bisTR suppresses hTG specific immune responses. These results indicate that hTG contains multiple epitopes that differentially affect oral tolerization. Tolerogenic epitopes reside within fragments h6TR and h7TR. The removal of @entity1496 , and presumably hormone, from h4bisTR converts an immunogenic epitope to a tolerogenic epitope.

Multiple fragments of @entity1 TG are capable of inducing oral tolerance to whole XXXX TG.

@entity19 :: ('10090', 'Species') :: ['Mice'] @entity1 :: ('9606', 'Species') :: ['human'] @entity1496 :: ('MESH:D007455', 'Chemical') :: ['iodine'] @entity1669 :: ('MESH:D013967', 'Disease') :: ['autoimmune thyroiditis']
@entity1 :: (9606,Species) :: ['human']
