Processing of Mycobacterium tuberculosis antigen 85B involves intraphagosomal formation of peptide-major histocompatibility complex II complexes and is inhibited by live bacilli that decrease phagosome maturation.
Processing of Mycobacterium tuberculosis antigen 85B involves intraphagosomal formation of peptide-major histocompatibility complex II complexes and is inhibited by live bacilli that decrease phagosome maturation.
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DOI：
10.1084/jem.194.10.1421
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发表时间：
2001-11-19
期刊：
影响因子：
--
通讯作者：
Harding CV
中科院分区：
文献类型：
--
作者：
Ramachandra L;Noss E;Boom WH;Harding CV
结核分枝杆菌(MTB)通过抑制吞噬小体成熟来促进其在巨噬细胞内的存活。控制结核分枝杆菌感染需要CD4T细胞反应和主要组织相容性复合体(MHC)II类(MHC-II)对结核分枝杆菌抗原(AGS)的处理。为了研究结核分枝杆菌抗原的吞噬过程，从干扰素-γ(干扰素-γ)激活的巨噬细胞中用差速离心法和Percoll密度梯度亚细胞分级法分离纯化了含有热灭活或活结核分枝杆菌的吞噬小体。流式细胞仪和Western印迹分析表明，MTB噬菌体获得溶酶体相关膜蛋白-1(LAMP-1)、MHC-II和H2-DM。用T杂交瘤细胞检测MTB-Ag85B(241-256)-I-Ab复合物。这些复合体最初(20分钟内)出现在吞噬小体中，随后(20分钟)出现在质膜上，但从未出现在晚期的内吞体内。巨噬细胞处理HK MTB比活MTB更快、更有效；含有活MTB的吞噬体比含HK MTB的吞噬体能表达更少的Ag85B(241-256)-I-Ab复合体。这是第一次对细菌Ag加工的研究，直接表明多肽-MHC-II复合体是在吞噬体内形成的，而不是在细菌AGS从吞噬体导出到内吞的Ag加工隔间后形成的。活的MTB可以改变吞噬小体的成熟，减少MHC-II抗原的加工，为MTB逃避免疫监视提供了一种机制，提高了它在宿主内的存活率。
Mycobacterium tuberculosis (MTB) inhibits phagosomal maturation to promote its survival inside macrophages. Control of MTB infection requires CD4 T cell responses and major histocompatibility complex (MHC) class II (MHC-II) processing of MTB antigens (Ags). To investigate phagosomal processing of MTB Ags, phagosomes containing heat-killed (HK) or live MTB were purified from interferon-γ (IFN-γ)–activated macrophages by differential centrifugation and Percoll density gradient subcellular fractionation. Flow organellometry and Western blot analysis showed that MTB phagosomes acquired lysosome-associated membrane protein-1 (LAMP-1), MHC-II, and H2-DM. T hybridoma cells were used to detect MTB Ag 85B(241–256)–I-Ab complexes in isolated phagosomes and other subcellular fractions. These complexes appeared initially (within 20 min) in phagosomes and subsequently (>20 min) on the plasma membrane, but never within late endocytic compartments. Macrophages processed HK MTB more rapidly and efficiently than live MTB; phagosomes containing live MTB expressed fewer Ag 85B(241–256)–I-Ab complexes than phagosomes containing HK MTB. This is the first study of bacterial Ag processing to directly show that peptide–MHC-II complexes are formed within phagosomes and not after export of bacterial Ags from phagosomes to endocytic Ag processing compartments. Live MTB can alter phagosome maturation and decrease MHC-II Ag processing, providing a mechanism for MTB to evade immune surveillance and enhance its survival within the host.
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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：
64.8
作者：
PETERS, PJ;NEEFJES, JJ;GEUZE, HJ
通讯作者：
GEUZE, HJ
影响因子：
7.8
作者：
Kleijmeer, MJ;Morkowski, S;Geuze, HJ
通讯作者：
Geuze, HJ
影响因子：
15.3
作者：
Clemens, DL;Horwitz, MA
通讯作者：
Horwitz, MA
影响因子：
5.4
作者：
HARDING, CV
通讯作者：
HARDING, CV