Fine dissection of a nine amino acid glycoprotein epitope, a major determinant recognized by lymphocytic choriomeningitis virus-specific class I-restricted H-2Db cytotoxic T lymphocytes.
Fine dissection of a nine amino acid glycoprotein epitope, a major determinant recognized by lymphocytic choriomeningitis virus-specific class I-restricted H-2Db cytotoxic T lymphocytes.
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对九种氨基酸糖蛋白表位的细剖析，这是由淋巴细胞脉络膜脑膜炎病毒特异性I类I限制的I限制的H-2DB细胞毒性T淋巴细胞识别的主要决定因素。
DOI：
10.1084/jem.168.2.559
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发表时间：
1988-08-01
影响因子：
15.3
通讯作者：
Tishon, A
中科院分区：
文献类型：
--
作者：
Oldstone, M B;Whitton, J L;Lewicki, H;Tishon, A
我们确定了VAL-GLU-ASN-PRO-GLY-GLY- TYR-CYS-LEU的9个氨基酸序列作为h -2b限制性CTL免疫识别淋巴细胞性脉络丛脑膜炎病毒（LCMV）的主要表位。利用分子遗传学和化学方法对病毒糖蛋白的aa残基278 ~ 286进行了精确鉴定。表位的组成特征是反向（β转），而不是两向的α螺旋。在VAL的278位有一个单一的aa被其他非极性（疏水）氨基酸（LEU， ILE， ALA或GLY）取代的一系列肽被识别该表位的CTL克隆识别和裂解。相比之下，用大的芳香氨基酸（增加了大量的：PHE， TYR）或极性侧链（SER， THR）取代VAL将通常识别aa 278-286的CTL克隆分离成两组，一组尽管发生这些变化仍保持裂解（允许），另一组不能裂解，表明CTL可以区分单个aa。通常，该位置的变化（VAL----ASP或GLU）会减少CTL裂解，而VAL改变为LYS或ASN对所分析的五个CTL克隆中的四个影响最小。CTL与病毒表位的反应性受鼠MHC单倍型的Db限制，而不受Kb限制。Db的16-aa肽横跨α 1残基37-52，可阻断CTL裂解，而对应的Kb肽与Db在第50位的单个aa不同，则不能阻断CTL裂解。
We define a nine-amino acid (aa) sequence of VAL-GLU-ASN-PRO-GLY-GLY- TYR-CYS-LEU as a major epitope for immunologic recognition of lymphocytic choriomeningitis virus (LCMV) by H-2b-restricted CTL. The epitope was characterized using molecular genetics to bracket broadly and chemistry to precisely identify aa residues 278-286 of the viral glycoprotein. The epitope's composition is characteristic of a reverse (beta turn) but not an amphipathic alpha helix. A series of peptides with a single aa substitution in position 278 of VAL with other nonpolar (hydrophobic) amino acids (LEU, ILE, ALA, or GLY) coat targets that are recognized and lysed by CTL clones recognizing this epitope. In contrast, substitution of VAL with either large aromatic amino acids (that add bulk: PHE, TYR) or polar side chains (SER, THR) segregates CTL clones normally recognizing aa 278-286 into two groups, one that remains lytic (permissive) despite these changes and another that fails to lyse, indicating CTL can discriminate at a single aa. A change in charge at this position (VAL----ASP or GLU), in general, reduces CTL lysis while a change of VAL to LYS or ASN has minimal affect for four of the five CTL clones analyzed. CTL reactivity with the viral epitope is restricted by the Db but not the Kb of the murine MHC haplotype. A 16-aa peptide of Db that spans alpha 1 residues 37-52 blocks CTL lysis, whereas the corresponding Kb peptide that differs from Db in a single aa in position 50 does not.