2012年10月13日 讯 /生物谷BIOON/ --10月11日，刊登在国际杂志Immunity上的一篇研究报告中，来自澳洲莫纳斯大学等处的研究者首次使得谷蛋白（粘胶质，gluten）和免疫系统的T细胞之间的相互作用可视化。这就为研究脂泻病带来了帮助，在133个人中，大约有1人会受到脂泻病的影响。
腹泻病（celiac disease）会影响小肠的消化过程，当腹泻病患者消化谷蛋白时，其机体免疫系统会触发T细胞来抵御外来蛋白质的入侵，这常常会损伤小肠功能，并且抑制机体影响的吸收过程。目前针对谷蛋白摄入引发的此疾病并无有效疗法。
文章中，研究者使用同步加速器研究了T细胞如何与谷蛋白进行作用，并对其进行了可视化操作，谷蛋白来自小麦、黑麦和大麦中。大约有一半人群对腹泻病存在遗传上的敏感性，因为其携带有免疫效应基因HLA-DQ2或HLA-DQ8。20人中至少有一人携带HLA-DQ2，而在150人中也至少有一人携带有HLA-DQ8基因，这就使得其更易患腹泻病。
后期研究中，研究者会深入研究确定携带HLA-DQ2基因的患者由于谷蛋白导致的T细胞激活，是否在携带HLA-DQ8基因的患者身上也遵循类似法则。研究者Anderson表示，因为我们知道谷蛋白肽可以对腹泻病产生效应，因此我们就可以追溯导致自身损伤免疫效应的一系列分子事件。（生物谷Bioon.com）
编译自：New Insight Into Celiac Disease
doi:10.1016/j.immuni.2012.07.013
PMC:
PMID:
Biased T Cell Receptor Usage Directed against Human Leukocyte Antigen DQ8-Restricted Gliadin Peptides Is Associated with Celiac Disease
Sophie E. Broughton, Jan Petersen, Alex Theodossis, Stephen W. Scally, Khai Lee Loh, Allan Thompson, Jeroen van Bergen, Yvonne Kooy-Winkelaar, Kate N. Henderson, Travis Beddoe, Jason A. Tye-Din, Stuart I. Mannering, Anthony W. Purcell, James McCluskey, Robert P. Anderson, Frits Koning, Hugh H. Reid, Jamie Rossjohn.
Celiac disease is a human leukocyte antigen (HLA)-DQ2- and/or DQ8-associated T cell-mediated disorder that is induced by dietary gluten. Although it is established how gluten peptides bind HLA-DQ8 and HLA-DQ2, it is unclear how such peptide-HLA complexes are engaged by the T cell receptor (TCR), a recognition event that triggers disease pathology. We show that biased TCR usage (TRBV9∗01) underpins the recognition of HLA-DQ8-α-I-gliadin. The structure of a prototypical TRBV9∗01-TCR-HLA-DQ8-α-I-gliadin complex shows that the TCR docks centrally above HLA-DQ8-α-I-gliadin, in which all complementarity-determining region-β (CDRβ) loops interact with the gliadin peptide. Mutagenesis at the TRBV9∗01-TCR-HLA-DQ8-α-I-gliadin interface provides an energetic basis for the Vβ bias. Moreover, CDR3 diversity accounts for TRBV9∗01+ TCRs exhibiting differing reactivities toward the gliadin epitopes at various deamidation states. Accordingly, biased TCR usage is an important factor in the pathogenesis of DQ8-mediated celiac disease. Biased T cell receptor usage is associated with DQ8-mediated celiac disease The structure of a prototypical TRBV9∗01-TCR-DQ8-α1-gliadin complex Only two residues within the TRBV9∗01 chain are required A TCR's deamidation dependence was associated with CDR3 variability.
