Induction of M3-restricted cytotoxic T lymphocyte responses by N-formylated peptides derived from Mycobacterium tuberculosis.
Induction of M3-restricted cytotoxic T lymphocyte responses by N-formylated peptides derived from Mycobacterium tuberculosis.
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DOI：
10.1084/jem.193.10.1213
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发表时间：
2001-05-21
期刊：
影响因子：
--
通讯作者：
Wang CR
中科院分区：
文献类型：
--
作者：
Chun T;Serbina NV;Nolt D;Wang B;Chiu NM;Flynn JL;Wang CR
主要组织相容性复合体(MHC)I类限制性CD8+T细胞在抗结核分枝杆菌(Mtb)保护性免疫中起重要作用。然而，目前仅有少数MHC-Ia类限制性CD8+T细胞识别的Mtb多肽被鉴定。关于Ib类限制性T细胞识别的表位的信息甚至更加有限。M3是一种MHC Ib类分子，优先向CD8+T细胞递送N-甲酰化的多肽。由于细菌用N-甲酰蛋氨酸启动蛋白质合成，M3独特的结合特异性使其特别适合呈现这些特定的细菌表位。我们已经扫描了Mtb基因组的全序列，寻找与其他M3结合肽有共同特征的NH2末端多肽。与这些序列相对应的合成肽在基于免疫荧光的肽结合试验中被测试其与M3结合的能力。其中4个N甲酰化的Mtb多肽能够从包被多肽的脾细胞免疫的小鼠中诱导出细胞毒性T淋巴细胞(CTL)。结核分枝杆菌多肽特异的M3限制性CTL能有效地裂解结核分枝杆菌感染的巨噬细胞，提示这些N甲酰化的结核分枝杆菌多肽是结核分枝杆菌感染细胞天然加工的表位。此外，来自结核分枝杆菌感染的肺、脾和淋巴结的T细胞对N-甲酰化的结核分枝杆菌多肽的反应是M3限制性的。综上所述，我们的数据提示M3限制性T细胞可能参与了对结核分枝杆菌的免疫反应。
Major histocompatibility complex (MHC) class I–restricted CD8+ T cells play a critical role in the protective immunity against Mycobacterium tuberculosis (Mtb). However, only a few Mtb peptides recognized by MHC class Ia–restricted CD8+ T cells have been identified. Information on epitopes recognized by class Ib–restricted T cells is even more limited. M3 is an MHC class Ib molecule that preferentially presents N-formylated peptides to CD8+ T cells. Because bacteria initiate protein synthesis with N-formyl methionine, the unique binding specificity of M3 makes it especially suitable for presenting these particular bacterial epitopes. We have scanned the full sequence of the Mtb genome for NH2-terminal peptides that share features with other M3-binding peptides. Synthetic peptides corresponding to these sequences were tested for their ability to bind to M3 in an immunofluorescence-based peptide-binding assay. Four of the N-formylated Mtb peptides were able to elicit cytotoxic T lymphocytes (CTLs) from mice immunized with peptide-coated splenocytes. The Mtb peptide–specific, M3-restricted CTLs lysed the Mtb-infected macrophages effectively, suggesting that these N-formylated Mtb peptides are presented as the naturally processed epitopes by Mtb-infected cells. Furthermore, T cells from Mtb-infected lungs, spleen, and lymph nodes responded to N-formylated Mtb peptides in an M3-restricted manner. Taken together, our data suggest that M3-restricted T cells may participate in the immune response to Mtb.
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影响因子：
3.1
作者：
HAVLIR, DV;WALLIS, RS;ELLNER, JJ
通讯作者：
ELLNER, JJ
影响因子：
32.4
作者：
Gulden, PH;Fischer, P;Pamer, EG
通讯作者：
Pamer, EG
DOI：
10.1084/jem.187.10.1633
发表时间：
1998-05-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lewinsohn DM;Alderson MR;Briden AL;Riddell SR;Reed SG;Grabstein KH
通讯作者：
Grabstein KH
影响因子：
32.4
作者：
Lenz, LL;Dere, B;Bevan, MJ
通讯作者：
Bevan, MJ
影响因子：
5.4
作者：
Braud, V;Jones, EY;McMichael, A
通讯作者：
McMichael, A