Differences in the risk of celiac disease associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation
Differences in the risk of celiac disease associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation
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DOI：
10.1038/ni.1780
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发表时间：
2009-10-01
影响因子：
30.5
通讯作者：
Sollid, Ludvig M.
中科院分区：
文献类型：
--
作者：
Fallang, Lars-Egil;Bergseng, Elin;Sollid, Ludvig M.
由抗谷蛋白T细胞反应驱动的乳糜泻与组织相容性抗原HLA-DQ 2.5密切相关，但与HLA-DQ 2.2几乎无关。然而，这些分子具有非常相似的肽结合基序，并且都存在谷蛋白T细胞表位。我们发现，相对于DQ 2.2（+）细胞，DQ 2.5（+）抗原呈递细胞（APC）具有更高的结合肽稳定性和延长的谷蛋白呈递。DQ 2.5保留其肽货物的能力提高可归因于DQ α 22的多态性，由此DQ 2.5（酪氨酸）可与肽主链建立氢键，但DQ 2.2（苯丙氨酸）不能。我们的研究结果表明，肽和主要组织相容性复合物（MHC）的复合物的动力学稳定性是重要的HLA与疾病的关联。
Celiac disease driven by an antigluten T cell response is strongly associated with the histocompatibility antigen HLA-DQ2.5 but is barely associated with HLA-DQ2.2. Yet these molecules have very similar peptide-binding motifs and both present gluten T cell epitopes. We found that DQ2.5(+) antigen-presenting cells (APCs) had greater stability of bound peptides and protracted gluten presentation relative to that of DQ2.2(+) cells. The improved ability of DQ2.5 to retain its peptide cargo can be ascribed to a polymorphism of DQ alpha 22 whereby DQ2.5 (tyrosine) can establish a hydrogen bond to the peptide main chain but DQ2.2 (phenylalanine) cannot. Our findings suggest that the kinetic stability of complexes of peptide and major histocompatibility complex (MHC) is of importance for the association of HLA with disease.