Jackson Nicola, Compton Evan, Trowsdale John, Kelly Adrian P
Division of Immunology, Department of Pathology, University of Cambridge, Cambridge, UK.
Eur J Immunol. 2014 Apr;44(4):962-9. doi: 10.1002/eji.201344065. Epub 2014 Feb 16.
Type B T cells recognize peptide-MHC class II (pMHCII) isoforms that are structurally distinct from those recognized by conventional type A T cells. These alternative type B conformers result from peptide loading in the absence of HLA-DM. Type A conformers are more stable than type B pMHCII conformers but bind the same peptide in the same register. Here, we show that interaction of Salmonella Typhimurium with bone marrow derived dendritic cells (BMDCs) isolated from C3H/HeNCr1 mice results in enhanced presentation of peptide Ag to type B T cells. The effect could be mimicked by purified PAMPs, the most potent of which were curdlan and zymosan, β-(1,3)-glucan-containing polymers that are recognized by Dectin-1. Blocking of Dectin-1 with Ab and laminarin inhibited the induction of the type B T-cell response by BMDCs, confirming its role as a PRR for S. Typhimurium. Splenic DCs (sDCs) expressed Dectin-1 but were refractive to the induction of type B responses by S. Typhimurium and curdlan. Type B T cells have been shown to escape thymic tolerance and to transfer pathology in an autoimmune disease model. The induction of type B responses by gram-negative bacteria provides a mechanism by which autoreactive T cells may be produced during infection.
B型T细胞识别的肽 - 主要组织相容性复合体II类（pMHCII）异构体在结构上与传统A型T细胞识别的异构体不同。这些替代性的B型构象是在没有HLA - DM的情况下肽负载产生的。A型构象比B型pMHCII构象更稳定，但以相同的序列结合相同的肽。在这里，我们表明鼠伤寒沙门氏菌与从C3H/HeNCr1小鼠分离的骨髓来源的树突状细胞（BMDC）相互作用导致肽抗原向B型T细胞的呈递增强。这种效应可以被纯化的病原体相关分子模式（PAMP）模拟，其中最有效的是可德胶和酵母聚糖，它们是含有β-（1,3）-葡聚糖的聚合物，可被Dectin-1识别。用抗体和海带多糖阻断Dectin-1可抑制BMDC对B型T细胞反应的诱导，证实了其作为鼠伤寒沙门氏菌模式识别受体（PRR）的作用。脾树突状细胞（sDC）表达Dectin-1，但对鼠伤寒沙门氏菌和可德胶诱导的B型反应无反应。已表明B型T细胞可逃避胸腺耐受性，并在自身免疫疾病模型中传递病理状态。革兰氏阴性菌对B型反应的诱导提供了一种机制，通过该机制在感染期间可能产生自身反应性T细胞。
