In vivo cytotoxic T lymphocyte elicitation by mycobacterial heat shock protein 70 fusion proteins maps to a discrete domain and is CD4(+) T cell independent.
In vivo cytotoxic T lymphocyte elicitation by mycobacterial heat shock protein 70 fusion proteins maps to a discrete domain and is CD4(+) T cell independent.
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分枝杆菌热休克蛋白70融合蛋白映射到离散结构域的体内细胞毒性T淋巴细胞诱导，并且与CD4（+）T细胞无关。
DOI：
10.1084/jem.191.2.403
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发表时间：
2000-01-17
影响因子：
15.3
通讯作者：
Young, R A
中科院分区：
文献类型：
--
作者：
Huang, Q;Richmond, J F;Suzue, K;Eisen, H N;Young, R A
为了深入了解可溶性热休克蛋白（hsp）融合体诱导CD 8+细胞毒性T淋巴细胞（CTL）对抗融合体伴侣的机制，解剖了结核分枝杆菌（Mycobacterium tuberculosis）hsp 70，以确定是否需要特定的hsp结构域，并使用敲除小鼠来确定融合蛋白的免疫原性是否依赖于CD 4 + T淋巴细胞。我们发现，诱导CD 8 + CTL的能力取决于一个离散的200个氨基酸的蛋白质结构域，这表明融合蛋白对CD 8 + T细胞的免疫原性不需要偶联的伴侣蛋白功能或肽结合。此外，我们发现卵清蛋白（OVA）. hsp 70融合蛋白在CD 4敲除和野生型C57 BL/6小鼠中以及在hsp 70为鼠（自身）来源时，均能诱导抗OVA CD 8 + CTL。hsp 70融合蛋白诱导CD 4非依赖性CTL应答的能力表明，hsp 70融合蛋白可用于针对CD 4 + T细胞缺陷个体的疾病的免疫预防和治疗。
To gain insights into the mechanisms by which soluble heat shock protein (hsp) fusions can elicit CD8+ cytotoxic T lymphocytes (CTLs) against the fusion partner, mycobacterial (Mycobacterium tuberculosis) hsp70 was dissected to ascertain whether a particular hsp domain is necessary, and knockout mice were used to determine whether the fusion protein's immunogenicity is dependent on CD4+ T lymphocytes. We found that the ability to elicit CD8+ CTLs depends on a discrete 200–amino acid protein domain, indicating that the fusion protein's immunogenicity for CD8+ T cells does not require coupled chaperone function or peptide binding. Further, we found that ovalbumin (OVA).hsp70 fusion protein elicited anti-OVA CD8+ CTLs about equally well in CD4 knockout and wild-type C57BL/6 mice, and also when the hsp70 was of murine (self) origin. The ability of hsp70 fusion proteins to elicit CD4-independent CTL responses suggests that hsp70 fusion proteins may be useful for immunological prophylaxis and therapy against disease in CD4+ T cell–deficient individuals.