Toward the assessment of food toxicity for celiac patients: characterization of monoclonal antibodies to a main immunogenic gluten peptide.
Toward the assessment of food toxicity for celiac patients: characterization of monoclonal antibodies to a main immunogenic gluten peptide.
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DOI：
10.1371/journal.pone.0002294
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发表时间：
2008-05-28
期刊：
影响因子：
3.7
通讯作者：
Sousa C
中科院分区：
文献类型：
--
作者：
Morón B;Bethune MT;Comino I;Manyani H;Ferragud M;López MC;Cebolla A;Khosla C;Sousa C
乳糜泻是一种永久性的对来自小麦、大麦、黑麦和一些患者的燕麦中的醇溶蛋白的不耐受。消化道中产生的部分消化的谷蛋白多肽会导致小肠发炎。使用针对这些免疫毒素多肽的单抗进行高通量、基于免疫的分析将有助于在食品中检测它们，并能够监测它们的酶解毒作用。针对一种免疫毒性很强的33肽，研制了两种单抗G12和A1。研究了每种抗体在定量检测乳糜泻患者的食物毒性方面的潜力。G12和A1抗体的表位偏好通过重组、合成或酶促来源的面筋蛋白多肽变体的酶联免疫吸附试验来确定。G12和A1抗体的识别序列分别为六聚体和七聚体表位。虽然G12对33-聚体的亲和力优于A1，但A1对面筋检测的敏感性更高。这一观察结果与醇溶蛋白中发现的A1表位比G12表位更多有关。面筋蛋白被谷氨酸酶消化后的T细胞活化程度与A1抗体检测到的完整多肽的激活程度相当。A1的多肽识别包括与乳糜泻的适应性免疫反应和先天免疫反应有关的醇溶蛋白多肽。A1抗体的敏感性和表位选择性有助于检测与面筋相关的多肽，推断食物对乳糜泻患者的潜在毒性，以及监测转谷氨酰胺酶2或谷氨酸酶对多肽的修饰。
Celiac disease is a permanent intolerance to gluten prolamins from wheat, barley, rye and, in some patients, oats. Partially digested gluten peptides produced in the digestive tract cause inflammation of the small intestine. High throughput, immune-based assays using monoclonal antibodies specific for these immunotoxic peptides would facilitate their detection in food and enable monitoring of their enzymatic detoxification. Two monoclonal antibodies, G12 and A1, were developed against a highly immunotoxic 33-mer peptide. The potential of each antibody for quantifying food toxicity for celiac patients was studied. Epitope preferences of G12 and A1 antibodies were determined by ELISA with gluten-derived peptide variants of recombinant, synthetic or enzymatic origin. The recognition sequences of G12 and A1 antibodies were hexameric and heptameric epitopes, respectively. Although G12 affinity for the 33-mer was superior to A1, the sensitivity for gluten detection was higher for A1. This observation correlated to the higher number of A1 epitopes found in prolamins than G12 epitopes. Activation of T cell from gluten digested by glutenases decreased equivalently to the detection of intact peptides by A1 antibody. Peptide recognition of A1 included gliadin peptides involved in the both the adaptive and innate immunological response in celiac disease. The sensitivity and epitope preferences of the A1 antibody resulted to be useful to detect gluten relevant peptides to infer the potential toxicity of food for celiac patients as well as to monitor peptide modifications by transglutaminase 2 or glutenases.
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影响因子：
15.3
作者：
Arentz-Hansen, H;Korner, R;Molberg, O;Quarsten, H;Vader, W;Kooy, Y M;Lundin, K E;Koning, F;Roepstorff, P;Sollid, L M;McAdam, S N
通讯作者：
McAdam, S N
影响因子：
29.4
作者：
Gianfrani, Carmen;Siciliano, Rosa A.;Rossi, Mauro
通讯作者：
Rossi, Mauro
影响因子：
56.9
作者：
Shan, L;Molberg, O;Khosla, C
通讯作者：
Khosla, C
DOI：
10.1124/jpet.106.104315
发表时间：
2006-09-01
影响因子：
3.5
作者：
Gass, Jonathan;Vora, Harmit;Khosla, Chaitan
通讯作者：
Khosla, Chaitan
影响因子：
5
作者：
ELLIS, HJ;FREEDMAN, AR;CICLITIRA, PJ
通讯作者：
CICLITIRA, PJ