TAP peptide transporter-independent presentation of heat-killed Sendai virus antigen on MHC class I molecules by splenic antigen-presenting cells.
TAP peptide transporter-independent presentation of heat-killed Sendai virus antigen on MHC class I molecules by splenic antigen-presenting cells.
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DOI：
10.4049/jimmunol.159.11.5364
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发表时间：
1997-12
影响因子：
4.4
通讯作者：
T. Liu;B. Chambers;A. Diehl;L. Van Kaer;M. Jondal;H. Ljunggren
中科院分区：
文献类型：
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作者：
T. Liu;B. Chambers;A. Diehl;L. Van Kaer;M. Jondal;H. Ljunggren
用热灭活的仙台病毒免疫 C57BL/6 (B6) 小鼠会产生仙台病毒特异性 CD8+ T 细胞反应。这表明 APC 具有吸收外源性（非复制性）仙台病毒 Ag 并将其呈递到 MHC I 类分子上的能力。关于这种形式的 Ag 的细胞内加工需求及其在 MHC I 类分子上的呈递知之甚少。因此，我们研究了热灭活的仙台病毒 Ag 在脾 APC 中 MHC I 类分子上的加工和呈递。热灭活的仙台病毒 Ag 可以被正常 B6 以及 TAP-1(-/-) 脾 APC 有效加工。呈递受到 I 类 MHC 限制，因为缺乏 I 类 MHC 表达的 TAP-1/beta2m-/- 小鼠的 APC 未观察到呈递。即使在存在布雷菲德菌素 A 的情况下也会出现呈递，但会被细胞松弛素 D 和氯喹阻断。最后，B6 以及 TAP-1(-/-) 脾 APC 在体外负载了热灭活的仙台病毒 Ag，在体内引发了幼稚 CD8+ T 细胞。这些研究表明，正常脾 APC 中 MHC I 类上存在 TAP 独立的 Ag 呈递途径，与 MHC II 类 Ag 呈递途径有许多相似之处。目前的结果讨论了 I 类 MHC 上外源 Ag 的加工和呈递背后的事件、病毒感染期间 CD8+ T 细胞启动的分子基础以及疫苗开发的前景。
Immunization of C57BL/6 (B6) mice with heat-killed Sendai virus generates a Sendai virus-specific CD8+ T cell response. This suggests that APC have the capacity to take up and present exogenous (nonreplicative) Sendai virus Ag on MHC class I molecules. Little is known about the intracellular requirements for processing of this form of Ag and its presentation on MHC class I. Therefore, we have studied the processing and presentation of heat-killed Sendai virus Ag on MHC class I molecules in splenic APC. Heat-killed Sendai virus Ags were efficiently processed by normal B6 as well as by TAP-1(-/-) splenic APC. Presentation was MHC class I restricted, since no presentation was seen by APC from TAP-1/beta2m-/- mice that lack expression of MHC class I. Presentation occurred even in the presence of brefeldin A, but was blocked by cytochalasin D as well as chloroquine. Finally, B6 as well as TAP-1(-/-) splenic APC, loaded with heat-killed Sendai virus Ag in vitro, primed naive CD8+ T cells in vivo. These studies suggest the existence of a TAP-independent pathway for Ag presentation on MHC class I in normal splenic APC, bearing many similarities with the MHC class II pathway for Ag presentation. The present results are discussed in relation to the events underlying the processing and presentation of exogenous Ag on MHC class I, the molecular basis for CD8+ T cell priming during viral infections, and prospects for vaccine development.