Amino acid residues in the T cell receptor CDR3 determine the antigenic reactivity patterns of insulin-reactive hybridomas.
Amino acid residues in the T cell receptor CDR3 determine the antigenic reactivity patterns of insulin-reactive hybridomas.
复制标题
T 细胞受体 CDR3 中的氨基酸残基决定胰岛素反应性杂交瘤的抗原反应模式。
DOI：
10.4049/jimmunol.146.10.3513
复制
发表时间：
1991
影响因子：
4.4
通讯作者：
N. Hozumi
中科院分区：
文献类型：
--
作者：
J. Wither;J. Pawling;L. Phillips;T. Delovitch;N. Hozumi
我们研究了TCR基因的使用在一组牛胰岛素/I-Ad限制性T细胞杂交瘤从BALB/c小鼠。这些杂交体表现出几种不同的反应模式，这些反应模式由它们对胰岛素物种变体的反应能力定义。TCR-α和β-基因的使用与这些反应模式的相关性表明，TCR基因的使用仅限于Ag反应性组内。特别是，V-J连接区（CDR 3等效物）受到TCR-α和TCR-β链中存在的保守连接氨基酸基序的限制。在表达相同的V α和V β基因片段但表现出不同反应模式的杂交体中比较TCR基因的使用，揭示了J α和/或J β基因片段使用的变化可以改变抗原反应性。事实上，CDR 3区域内的单个或有限的氨基酸差异足以显著改变精细特异性。这些数据证明了CDR 3在决定牛肉胰岛素反应性杂交体中的抗原反应性中的关键作用，并且与TCR/肽/MHC相互作用的当前模型相容。
We examined TCR gene usage in a panel of beef insulin/I-Ad-restricted T cell hybrids obtained from BALB/c mice. These hybrids demonstrated several distinct patterns of reactivity defined by their ability to respond to species variants of insulin. Correlation of TCR-alpha and -beta-gene usage with these patterns of reactivity demonstrated that TCR gene usage was restricted within Ag reactivity groups. In particular, V-J junctional regions (CDR3 equivalent) were restricted with conserved junctional amino acid motifs present in both TCR-alpha- and -beta-chains. Comparison of TCR gene usage in hybrids expressing identical V alpha and V beta gene segments but demonstrating different patterns of reactivity revealed that changes in either J alpha and/or J beta gene segment usage could alter antigenic reactivity. Indeed, single or limited amino acid differences within the CDR3 region were sufficient to markedly alter fine specificity. These data demonstrate the critical role for CDR3 in determining antigenic reactivity in beef insulin-reactive hybrids and are compatible with the current model of TCR/peptide/MHC interaction.