A frameshift mutation at the NH2 terminus of the nucleoprotein gene does not affect generation of cytotoxic T lymphocyte epitopes.
A frameshift mutation at the NH2 terminus of the nucleoprotein gene does not affect generation of cytotoxic T lymphocyte epitopes.
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DOI：
10.4049/jimmunol.147.8.2697
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发表时间：
1991-10
影响因子：
4.4
通讯作者：
J. Fetten;N. Roy;E. Gilboa
中科院分区：
文献类型：
--
作者：
J. Fetten;N. Roy;E. Gilboa
编码流感病毒核蛋白（NP）基因的逆转录病毒载体感染的BALB/3T3细胞被在BALB/c小鼠（H-2d背景）中产生的CTL有效地裂解。含有NH2端移码突变（NPm）的NP突变体转导的细胞不表达生化检测水平的蛋白质，但仍能高效地向CTL呈递Ag。冷靶抑制研究表明，在携带NP或NPm的细胞中可以识别相同的CTL表位。在C3H小鼠（H-2k背景）中，转染NPm基因的L929细胞也能有效地向CTL呈递Ag。基因改造后表达5- 15倍低水平野生型NP的细胞不能向CTL呈递Ag，这反驳了CTL能够裂解表达极低水平Ag的细胞的观点，这可能是由于NPm中移码突变的抑制。在一类mhc限制性免疫反应表位生成机制的意义被考虑。
BALB/3T3 cells infected with a retroviral vector encoding the influenza virus nucleoprotein (NP) gene are efficiently lysed by CTL generated in BALB/c mice (H-2d background). Cells transduced with a mutant form of NP which contains a frameshift mutation at its NH2 terminus (NPm) do not express biochemically detectable levels of protein but nevertheless present Ag to CTL with high efficiency. Cold target inhibition studies indicate that the same CTL epitope(s) are recognized in cells harboring NP or NPm. L929 cells transduced with the NPm gene also present Ag efficiently to CTL raised in C3H mice (H-2k background). Cells engineered to express 5- to 15-fold lower levels of wild-type NP were not capable of presenting Ag to CTL, arguing against the notion that CTL are able to lyse cells expressing very low levels of Ag which might have resulted from suppression of the frameshift mutation in NPm. Implications to the mechanism of epitope generation in class I MHC-restricted immune responses are considered.