Receptor-mediated uptake of antigen/heat shock protein complexes results in major histocompatibility complex class I antigen presentation via two distinct processing pathways.
Receptor-mediated uptake of antigen/heat shock protein complexes results in major histocompatibility complex class I antigen presentation via two distinct processing pathways.
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DOI：
10.1084/jem.191.11.1957
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发表时间：
2000-06-05
期刊：
影响因子：
--
通讯作者：
Germain RN
中科院分区：
文献类型：
--
作者：
Castellino F;Boucher PE;Eichelberg K;Mayhew M;Rothman JE;Houghton AN;Germain RN
来源于肿瘤或病毒感染细胞的热休克蛋白（HSPs）可以在体内和体外刺激抗原特异性CD8+ T细胞反应。虽然已知这种抗原性是由主要组织相容性复合体（MHC） I类分子呈递给免疫系统的热刺蛋白相关肽引起的，但这种呈递过程背后的细胞生物学仍然知之甚少。在这里，我们发现hsp70通过一种具有饱和受体系统特征的机制结合到抗原提呈细胞表面。在这种膜相互作用之后，热休克蛋白相关抗原的加工和MHC I类递呈可以通过细胞质（与抗原加工相关的转运体[TAP]和蛋白酶体依赖）或内体（TAP和蛋白酶体独立）途径发生，首选途径由热休克蛋白相关物质中最佳抗原肽的序列背景决定。这些发现不仅表征了两种高效、特异的途径将热刺蛋白相关抗原转化为CD8+ T细胞的配体，而且还暗示了受体促进热刺蛋白或热刺蛋白相关配体从质膜或内体腔进入细胞质溶胶的跨膜转运机制的存在。
Heat shock proteins (HSPs) derived from tumors or virally infected cells can stimulate antigen-specific CD8+ T cell responses in vitro and in vivo. Although this antigenicity is known to arise from HSP-associated peptides presented to the immune system by major histocompatibility complex (MHC) class I molecules, the cell biology underlying this presentation process remains poorly understood. Here we show that HSP 70 binds to the surface of antigen presenting cells by a mechanism with the characteristics of a saturable receptor system. After this membrane interaction, processing and MHC class I presentation of the HSP-associated antigen can occur via either a cytosolic (transporter associated with antigen processing [TAP] and proteasome–dependent) or an endosomal (TAP and proteasome–independent) route, with the preferred pathway determined by the sequence context of the optimal antigenic peptide within the HSP-associated material. These findings not only characterize two highly efficient, specific pathways leading to the conversion of HSP-associated antigens into ligands for CD8+ T cells, they also imply the existence of a mechanism for receptor-facilitated transmembrane transport of HSP or HSP-associated ligands from the plasma membrane or lumen of endosomes into the cytosol.
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与热休克蛋白70混合的淋巴细胞绒毛膜炎病毒肽的免疫接种可导致保护性抗病毒药免疫和特异性细胞毒性T淋巴细胞。
DOI：
10.1084/jem.187.5.685
发表时间：
1998-03-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ciupitu AM;Petersson M;O'Donnell CL;Williams K;Jindal S;Kiessling R;Welsh RM
通讯作者：
Welsh RM
影响因子：
32.4
作者：
CASTELLINO, F;GERMAIN, RN
通讯作者：
GERMAIN, RN
影响因子：
56.9
作者：
KOVACSOVICSBANKOWSKI, M;ROCK, KL
通讯作者：
ROCK, KL
影响因子：
11.4
作者：
Lindner, R;Unanue, ER
通讯作者：
Unanue, ER
DOI：
10.1084/jem.189.9.1437
发表时间：
1999-05-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chandawarkar RY;Wagh MS;Srivastava PK
通讯作者：
Srivastava PK