33-mer alpha-gliadin peptide (33-mer) (33-mer)

The 33-mer gliadin peptide is a 33-amino acid fragment (LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF) derived from alpha-gliadin, a major component of wheat gluten [1]. It is widely regarded as the primary immunodominant peptide responsible for the pathogenesis of Celiac Disease due to its extreme resistance to human digestive proteases [1, 2]. This resistance stems from its high proline and glutamine content, which prevents cleavage by gastric, pancreatic, and intestinal brush-border enzymes [3]. Upon entering the intestinal lamina propria, the peptide is deamidated by tissue transglutaminase 2 (tTG2), significantly increasing its binding affinity for HLA-DQ2 and HLA-DQ8 molecules on antigen-presenting cells [4]. This interaction triggers a robust T-cell mediated inflammatory response, leading to intestinal villous atrophy and malabsorption [2, 5]. Current pharmacological strategies targeting the 33-mer peptide focus on oral enzyme replacement therapies, such as Latiglutenase and TAK-062, which are designed to digest the peptide into non-toxic fragments before it can trigger an immune response [6, 7]. These therapies aim to mitigate the effects of accidental gluten consumption in patients adhering to a gluten-free diet [6]. [1] Shan L, et al. Science. 2002;297(5590):2275-9. [2] Tye-Din JA, et al. Sci Transl Med. 2010;2(41):41ra51. [3] Bethune MT, Khosla C. Methods Enzymol. 2008;434:255-71. [4] Molberg O, et al. Nat Med. 1998;4(6):713-7. [5] Sollid LM. Nat Rev Immunol. 2002;2(9):647-55. [6] Syage JA, et al. Dig Dis Sci. 2017;62(5):1277-85. [7] Pultz IS, et al. Gastroenterology. 2021;161(1):166-176.

Other names

alpha-gliadin (57-89)p57-8933-mer peptideLQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPFalpha-2 gliadin (57-89)

Proteolytic degradation of the immunodominant 33-mer peptide into smaller, non-toxic fragments by exogenous enzymes to prevent T-cell activation.