2012年10月13日 訊 /生物谷BIOON/ --10月11日,，刊登在國(guó)際雜志Immunity上的一篇研究報(bào)告中,，來自澳洲莫納斯大學(xué)等處的研究者首次使得谷蛋白（粘膠質(zhì)，gluten）和免疫系統(tǒng)的T細(xì)胞之間的相互作用可視化,。這就為研究脂瀉病帶來了幫助,，在133個(gè)人中，大約有1人會(huì)受到脂瀉病的影響,。
腹瀉?。╟eliac disease）會(huì)影響小腸的消化過程，當(dāng)腹瀉病患者消化谷蛋白時(shí),，其機(jī)體免疫系統(tǒng)會(huì)觸發(fā)T細(xì)胞來抵御外來蛋白質(zhì)的入侵,，這常常會(huì)損傷小腸功能，并且抑制機(jī)體影響的吸收過程,。目前針對(duì)谷蛋白攝入引發(fā)的此疾病并無有效療法,。
文章中，研究者使用同步加速器研究了T細(xì)胞如何與谷蛋白進(jìn)行作用,，并對(duì)其進(jìn)行了可視化操作,，谷蛋白來自小麥、黑麥和大麥中,。大約有一半人群對(duì)腹瀉病存在遺傳上的敏感性,，因?yàn)槠鋽y帶有免疫效應(yīng)基因HLA-DQ2或HLA-DQ8。20人中至少有一人攜帶HLA-DQ2,，而在150人中也至少有一人攜帶有HLA-DQ8基因,，這就使得其更易患腹瀉病。
后期研究中,，研究者會(huì)深入研究確定攜帶HLA-DQ2基因的患者由于谷蛋白導(dǎo)致的T細(xì)胞激活,，是否在攜帶HLA-DQ8基因的患者身上也遵循類似法則。研究者Anderson表示,，因?yàn)槲覀冎拦鹊鞍纂目梢詫?duì)腹瀉病產(chǎn)生效應(yīng),，因此我們就可以追溯導(dǎo)致自身損傷免疫效應(yīng)的一系列分子事件。（生物谷Bioon.com）
編譯自：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.
