Adjuvanticity of α2-macroglobulin, an independent ligand for the heat shock protein receptor CD91
Adjuvanticity of α2-macroglobulin, an independent ligand for the heat shock protein receptor CD91
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DOI：
10.4049/jimmunol.166.8.4968
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发表时间：
2001-04-15
影响因子：
4.4
通讯作者：
Srivastava, PK
中科院分区：
文献类型：
--
作者：
Binder, RJ;Karimeddini, D;Srivastava, PK
我们最近已经确定了CD 91作为热休克蛋白gp 96的受体。CD 91最初被鉴定为α 2-巨球蛋白（α M-2）的受体。Gp 96和α M-2都是CD 91的配体。因为gp 96-伴侣肽可以引发CD 8（+）T细胞应答并由APC重新呈递，所以我们测试了α M-2的类似性质。我们的研究表明，α M-2在体外结合肽，并且由α M-2陪伴的肽在用α M-2-肽复合物免疫的小鼠中有效地引发肽特异性CD 8（+）T细胞应答。此外，由α M-2陪伴的肽，如由gp 96陪伴的肽，可以由CD 91（+）APC在其MHC I分子上重新呈递。这些研究表明，α M-2分子，像热休克蛋白分子一样，是T细胞佐剂，可以将外源性Ag引导到Ag呈递的内源性途径中。细胞内分子伴侣和细胞外血清分子伴侣之间的显著相似性可能具有有趣的生理学分支。
We recently have identified CD91 as a receptor for the heat shock protein gp96. CD91 was identified initially as a receptor for alpha (2)-macroglobulin (alpha M-2). Gp96 and alpha M-2 are both ligands for CD91. Because gp96-chaperoned peptides can prime CD8(+) T cell responses and are re-presented by APCs, we tested alpha M-2 for similar properties. Our studies show that alpha M-2 binds peptides in vitro and that the peptides, chaperoned by alpha M-2, efficiently prime peptide-specific CD8(+) T cell responses in mice immunized with alpha M-2-peptide complexes. Furthermore, peptides chaperoned by alpha M-2 like those chaperoned by gp96, can be re-presented by CD91(+) APCs on their MHC I molecules. These studies demonstrate that alpha M-2 molecules, like the heat shock protein molecules, are T cell adjuvants that can channel exogenous Ags into the endogenous pathway of Ag presentaion. The remarkable similarities between an intracellular chaperone and an extracellular serum chaperone may have interesting physiological ramifications.