Cutting edge: CD91-independent cross-presentation of GRP94(gp96)-associated peptides
Cutting edge: CD91-independent cross-presentation of GRP94(gp96)-associated peptides
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DOI：
10.4049/jimmunol.168.9.4282
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发表时间：
2002-05-01
影响因子：
4.4
通讯作者：
Nicchitta, CV
中科院分区：
文献类型：
--
作者：
Berwin, B;Hart, JP;Nicchitta, CV
GRP 94（gp 96）增强CD 8（+）T细胞对其结合肽的应答，这一过程需要其相关肽进入APC的MHC I类交叉呈递途径。进入该途径需要受体介导的内吞作用，并且已报道CD 91（低密度脂蛋白受体相关蛋白）是介导GRP 94摄取进入APC的受体。然而，CD 91在基于分子伴侣的肽Ag再呈递中的直接作用尚未得到证实。我们研究了CD 91对GRP 94细胞表面结合、内化和在APC中运输的贡献。尽管很容易获得CD 91在α 2-巨球蛋白结合和摄取中的明确作用，但加入过量的CD 91配体、活化的α 2-巨球蛋白或受体相关蛋白（所有已知CD 91配体的拮抗剂）不影响GRP 94细胞表面结合、受体介导的内吞作用或肽再呈递。这些数据鉴定了在肽Ag再呈递中起作用的不依赖于CD 91的GRP 94内化途径。
GRP94(gp96) elicits CD8(+) T cell responses against its bound peptides, a process requiring access of its associated peptides into the MHC class I cross-presentation pathway of APCs. Entry into this pathway requires receptor-mediated endocytosis, and CD91 (low-density lipoprotein receptor-related protein) has been reported to be the receptor mediating GRP94 uptake into APC. However, a direct role for CD91 in chaperone-based peptide Ag re-presentation has not been demonstrated. We investigated the contribution of CD91 to GRP94 cell surface binding, internalization, and trafficking in APCs. Whereas a clear role for CD91 in alpha(2)-macroglobulin binding and uptake was readily obtained, the addition of excess CD91 ligand, activated a2-macroglobulin, or receptor-associated protein, an antagonist of all known CD91 ligands, did not affect GRP94 cell surface binding, receptor-mediated endocytosis, or peptide re-presentation. These data identify a CD91-independent, GRP94 internalization pathway that functions in peptide Ag re-presentation.