Unlike most other dietary proteins, gluten is incompletely digested by gastrointestinal proteases, yielding proteolytically resistant peptides that trigger a deleterious immune response in genetically susceptible individuals. To widely varying degrees in celiac patients, this immune response produces intestinal effects, such as mucosal damage, malabsorption, and clinical diarrhea, as well as systemic humoral effects, such as the production of anti-gliadin antibodies and anti-transglutaminase 2 autoantibodies. The only existing therapy for celiac disease is a gluten-free diet, which is effective in most celiac patients when strictly followed. However, the maintenance of this diet is extremely difficult due to the ubiquity of gluten in most human diets, and relapse due to accidental ingestion of gluten contained in inadequately labeled or glutencontaminated foods is an abiding concern and a frequent occurrence for treated celiac patients. Several properties of immunogenic gluten peptides have been identified as being critical toward their pathogenic role in celiac disease. These include proteolytic resistance due to high proline and glutamine content, presence of preferred glutamine residues for TG2-mediated glutamine deamidation, and high affinity of these deamidated sequences for human leukocyte antigen -DQ2, a class II major histocompatibility complex molecule associated with over 90% of diagnosed celiac patients. Additionally, longer peptides containing multiple epitopes appear to be more immunotoxic than their constituent epitopes. One peptide in particular, a 33-mer derived from in vitro gastrointestinal proteolysis of a2-gliadin, possesses all of these characteristics and activates proliferation in all celiac patient-derived T cell lines tested so far. Moreover, this peptide is detected as a stable digestive product of ingested gluten in both rats and cynomolgus monkeys, suggesting it is likely produced from dietary gluten in the human gut as well. It is therefore presumed that the 33-mer is important in the induction and propagation of the adverse response to gluten in celiac disease patients. To enact such a role in vivo, however, this relatively large peptide must be transported intact across the mucosal epithelium to the underlying lymphoid tissue where it can be presented by DQ2 on antigen presenting cells to gluten-specific CD4+ T cells. Despite strong evidence implicating gluten peptides in celiac disease pathogenesis, the detection of a chemically-defined gluten peptide in extra-intestinal body fluids following oral dosing has yet to be reported, and the extent to which disease state alters permeability toward such a peptide is unclear. It is well established that active enteropathy is associated with structurally altered tight junctions and increased permeability toward small non-permeating molecules, and that these defects are not completely resolved by a gluten-free diet. However, it is unclear whether these findings will translate to increased permeability toward gluten peptides of sufficient size to elicit an immune response. Further, studies of intestinal permeability with respect to disease state in celiac patients are hampered by the practical difficulty of ensuring strict dietary exclusion of gluten. An animal model of gluten sensitivity could enable the observation and study of transepithelial gluten peptide delivery in an in vivo system in which dietary gluten content can be absolutely controlled. Furthermore, such an animal model could facilitate preclinical testing of pharmacological therapies aimed at protecting celiac patients from the constant risk of dietary gluten exposure. In a previous report, we characterized a condition of gluten sensitivity in juvenile rhesus macaques that is similar in many respects to celiac disease. Affected animals exhibited intestinal lesions, malabsorptive steatorrhea, clinical diarrhea, and elevated anti-gliadin antibodies in response to a gluten-containing diet. Administration of a gluten-free diet to one such affected animal, FH09, FG-4592 caused complete remission, whereas reintroduction of dietary gluten caused clinical, histological, and serological relapse. Similar dietary changes had no effect on an age-matched control, FR26. In this report, we Y-27632 conduct two pilot studies using the glutensensitive macaque model.