Characterization of the delayed type hypersensitivity-inducing epitope of MPT64 from Mycobacterium tuberculosis
Characterization of the delayed type hypersensitivity-inducing epitope of MPT64 from Mycobacterium tuberculosis
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DOI：
10.1046/j.1365-3083.1997.d01-429.x
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发表时间：
1997-05-01
影响因子：
3.7
通讯作者：
Haslov, K
中科院分区：
文献类型：
--
作者：
Oettinger, T;Holm, A;Haslov, K
结核分枝杆菌分泌几种蛋白质进入细胞外环境，其中一些仅限于结核分枝杆菌复合体。其中一种抗原是MPT64。最近，作者表明，本地和重组MPT64能够区分结核分枝杆菌感染和BCG丹麦1331疫苗接种。结核分枝杆菌感染引起的结核菌素纯化蛋白衍生物（PPD）敏感性与卡介苗接种或环境分枝杆菌感染引起的敏感性之间更好的区分将有助于结核病的控制。在这项研究中，作者报告了利用合成肽在接种了丹麦BCG 1331或东京BCG的豚鼠中定位和表征了一个dth诱导表位。利用重叠合成肽的研究已经确定了MPT64羧基末端的单个dth诱导表位的生物活性，该表位由位于核心表位（CE15） gy -173和Ala-187氨基酸之间的15个残基组成。使用CE15的截断版本进行精细定位表明，表位仅限于Val-174至glu186氨基酸之间的13个残基。而CE15的Dth反应性最佳。对CE15的不同修饰表明，赖氨酸树结构将皮肤反应性提高到接近结核菌素PPD反应性的最大水平。
Mycobacterium tuberculosis secretes several proteins into the extracellular environment, some of which are restricted to the M. tuberculosis complex. One of these antigens is MPT64. Recently, the authors showed that native as well as recombinant MPT64 is able to distinguish between an M. tuberculosis infection and a BCG Danish 1331 vaccination. Improved distinction between tuberculin purified protein derivative (PPD) sensitivity conferred by an M. tuberculosis infection and that induced by a BCG vaccination or infection with environmental mycobacteria would be useful in the control of tuberculosis. In this study, the authors report the mapping and characterization of a Dth-inducing epitope by the use of synthetic peptides in guinea-pigs vaccinated with BCG Danish 1331 or Tokyo. Studies with overlapping synthetic peptides have pinpointed the biological activity to a single Dth-inducing epitope at the carboxyterminal region of MPT64 consisting of 15 residues between amino acids Gly-173 and Ala-187, the core epitope (CE15). A fine mapping using truncated versions of CE15 indicates the epitope is restricted to 13 residues between amino acids Val-174 to Glu-186. However, the optimal Dth reactivity is obtained by CE15. Different modifications of CE15 revealed that a lysine tree construction improves the skin reactivity to a maximum level approaching that of the reactivity to tuberculin PPD.