IMMUNODOMINANCE OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED INFLUENZA-VIRUS EPITOPES CAN BE INFLUENCED BY THE T-CELL RECEPTOR REPERTOIRE
IMMUNODOMINANCE OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED INFLUENZA-VIRUS EPITOPES CAN BE INFLUENCED BY THE T-CELL RECEPTOR REPERTOIRE
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DOI：
10.1128/jvi.69.12.7416-7422.1995
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发表时间：
1995-12-01
影响因子：
5.4
通讯作者：
BLACKMAN, MA
中科院分区：
文献类型：
--
作者：
DALY, K;NGUYEN, P;BLACKMAN, MA
我们使用T细胞受体β链转基因小鼠来确定在流感病毒感染过程中，有限的T细胞受体谱系对主要组织相容性复合体I类限制性表位选择的影响。对野生型和转基因小鼠产生的T细胞杂交瘤的分析表明，识别的病毒表位取决于可用的T细胞受体谱系。野生型T细胞杂交瘤识别来自核蛋白和碱性聚合酶分子的表位，而从转基因小鼠产生的杂交瘤识别来自非结构蛋白和基质蛋白的表位，两组杂交瘤之间在特异性上没有重叠。在从流感病毒感染小鼠的肺部分离的支气管肺泡灌洗液细胞的细胞毒性测试中，这种特异性的互换模式也很明显。转基因杂交瘤中T细胞受体的使用非常有限，只有一个Vα元件用于识别的两个病毒表位中的每一个。在对非结构蛋白有反应的杂交瘤中，序列分析表明它们都表达与相同连接氨基酸(Leu-Leu)相关的Vα4Jα32链，这些连接氨基酸由5个不同的核苷酸序列编码，表明对T细胞受体的使用具有很强的选择性。综合这些数据，这些数据表明，在病毒感染过程中，可用的T细胞受体谱系可以对I类限制性表位的免疫优势产生深远影响。
We have used T-cell receptor beta-chain transgenic mice to determine the effects of a limited T-cell receptor repertoire on major histocompatibility complex class I-restricted epitope selection during the course of an influenza virus infection. Analysis of T-cell hybridomas generated from wild-type and transgenic mice demonstrated that the viral epitope recognized depended on the available T-cell receptor repertoire. Wild-type T-cell hybridomas recognized epitopes derived from the nucleoprotein and basic polymerase molecules, whereas hybridomas generated from transgenic mice recognized epitopes derived from the nonstructural protein and the matrix protein, There was no overlap in specificity between the two panels of hybridomas. This reciprocal pattern of specificity was also apparent in cytotoxicity assays with bronchoalveolar lavage cells isolated from the lungs of influenza virus-infected mice. T-cell receptor usage in the transgenic hybridomas was very restricted, with only one V alpha element used for each of the two viral epitopes recognized. In the case of the hybridomas reactive to the nonstructural protein, sequence analysis showed that they all expressed V alpha 4J alpha 32 chains associated with the same junctional amino acids (Leu-Leu) that were encoded by five different nucleotide sequences, indicating a strong selection for T-cell receptor usage, Taken together, these data demonstrate that the available T-cell receptor repertoire can have a profound effect on the immunodominance of class I-restricted epitopes during a viral infection.