Analysis of cytotoxic T cell responses to dominant and subdominant epitopes during acute and chronic lymphocytic choriomeningitis virus infection.
Analysis of cytotoxic T cell responses to dominant and subdominant epitopes during acute and chronic lymphocytic choriomeningitis virus infection.
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DOI：
10.4049/jimmunol.157.12.5543
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发表时间：
1996-12
影响因子：
4.4
通讯作者：
R. V. D. Most;A. Sette;C. Oseroff;J. Alexander;K. Murali-Krishna;Lisa. L. Lau;S. Southwood;J. Sidney;R. Chesnut;M. Matloubian;R. Ahmed
中科院分区：
文献类型：
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作者：
R. V. D. Most;A. Sette;C. Oseroff;J. Alexander;K. Murali-Krishna;Lisa. L. Lau;S. Southwood;J. Sidney;R. Chesnut;M. Matloubian;R. Ahmed
在BALB/c（H-2d）小鼠中针对淋巴细胞性脉络丛脑膜炎病毒（LCMV）的细胞毒性T细胞应答主要针对病毒核蛋白（NP 118 -126）中的单个免疫显性LD限制性表位。在这里，我们报告说，这种肽的免疫优势，可以部分归因于其非常高的亲和力LD I类分子。通过采用模体搜索和敏感的MHC I类结合试验，我们还确定了5个Kd结合肽的病毒核蛋白和糖蛋白中的16个Kd模体拟合肽。核蛋白和糖蛋白序列也包含18个Dd基序拟合肽，其中三个结合Dd的亲和力较弱。来自病毒糖蛋白的两个Kd结合肽，残基99-108和残基283-291，是亚显性表位。虽然这些肽并不敏化靶细胞的直接体外杀伤的主要抗病毒CTL，二级反应对这些肽很容易检测到急性LCMV感染后的BALB/c小鼠。清除了长期LCMV感染的BALB/c小鼠对这些亚显性表位表现出更持续的CTL应答，表明亚显性应答可能在清除慢性感染中发挥作用。亚显性表位之一，GP 283 -291，赋予肽疫苗接种后对持续性病毒感染的部分保护。
The cytotoxic T cell response against lymphocytic choriomeningitis virus (LCMV) in BALB/c (H-2d) mice is predominantly directed against a single immunodominant Ld-restricted epitope in the viral nucleoprotein (NP118-126). Here we report that the immunodominance of this peptide can be in part attributed to its very high affinity for Ld class I molecules. By employing motif searches and sensitive MHC class I binding assays, we also identified 5 Kd-binding peptides in the viral nucleoprotein and glycoprotein among 16 Kd motif-fitting peptides. The nucleoprotein and glycoprotein sequences also contained 18 Dd motif-fitting peptides, three of which bound Dd with weak affinity. Two of the Kd-binding peptides, residues 99-108 and residues 283-291 from the viral glycoprotein, are subdominant epitopes. Although these peptides did not sensitize target cells for direct ex vivo killing by primary antiviral CTL, secondary responses against these peptides were readily detected in BALB/c mice after acute LCMV infection. BALB/c mice that had cleared a long-term LCMV infection showed more sustained CTL responses against these subdominant epitopes, suggesting that subdominant responses might play a role in clearance of chronic infections. One of the subdominant epitopes, GP283-291, conferred partial protection against persistent viral infection after peptide vaccination.