Isolation of a distinct Mycobacterium tuberculosis mannose-capped lipoarabinomannan isoform responsible for recognition by CD1b-restricted T cells
Isolation of a distinct Mycobacterium tuberculosis mannose-capped lipoarabinomannan isoform responsible for recognition by CD1b-restricted T cells
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DOI：
10.1093/glycob/cws078
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发表时间：
2012-08-01
期刊：
影响因子：
4.3
通讯作者：
Chatterjee, Delphi
中科院分区：
文献类型：
--
作者：
Torrelles, Jordi B.;Sieling, Peter A.;Chatterjee, Delphi
甘露糖帽阿拉伯甘露聚糖(ManLAM)是一种复杂的脂多糖，广泛存在于结核分枝杆菌细胞膜中。许多生物学特性都归因于ManLAM，从直接与宿主相互作用并参与结核分枝杆菌的细胞内生存，到触发先天性和获得性免疫反应，包括激活CD1b限制性T细胞。由于其结构的复杂性，ManLAM被认为是一个不同的分子群体，这可能解释了它不同的生物学特性。ManLAM中的各种修饰如脂肪酸、琥珀酸、乳酸、磷脂酰肌醇和甲硫氧基糖的存在已被证明与其生物学活性直接相关，并可能参与CD1b与T细胞群之间的相互作用。为了进一步阐明参与CD1b限制性T细胞识别的ManLAM表位，以及它们在介导结核分枝杆菌感染免疫反应中的潜在作用，我们建立了一种方法，根据不同的等电值将ManLAM分解为八种不同的亚型。我们的结果表明，等电值为5.8的ManLAM亚型在刺激不同CD1b限制性T细胞系产生干扰素-γ方面最有效。对这些亚型ManLAM的组成分析表明，ManLAM分子的总电荷与其通过CD1呈递给T细胞的能力之间存在直接关系。
Mannose-capped lipoarabinomannan (ManLAM) is a complex lipoglycan abundantly present in the Mycobacterium tuberculosis cell envelope. Many biological properties have been ascribed to ManLAM, from directly interacting with the host and participating in the intracellular survival of M. tuberculosis, to triggering innate and adaptive immune responses, including the activation of CD1b-restricted T cells. Due to its structural complexity, ManLAM is considered a heterogeneous population of molecules which may explain its different biological properties. The presence of various modifications such as fatty acids, succinates, lactates, phosphoinositides and methylthioxylose in ManLAM have proven to correlate directly with its biological activity and may potentially be involved in the interactions between CD1b and the T cell population. To further delineate the specific ManLAM epitopes involved in CD1b-restricted T cell recognition, and their potential roles in mediating immune responses in M. tuberculosis infection, we established a method to resolve ManLAM into eight different isoforms based on their different isoelectric values. Our results show that a ManLAM isoform with an isoelectric value of 5.8 was the most potent in stimulating the production of interferon-gamma in different CD1b-restricted T-cell lines. Compositional analyses of these isoforms of ManLAM revealed a direct relationship between the overall charge of the ManLAM molecule and its capacity to be presented to T cells via the CD1 compartment.