The orientation and nature of the interaction between beef insulin-specific TCRs and the insulin/class II MHC complex.
The orientation and nature of the interaction between beef insulin-specific TCRs and the insulin/class II MHC complex.
复制标题
牛肉胰岛素特异性 TCR 与胰岛素/II 类 MHC 复合体之间相互作用的方向和性质。
作者：
J. Wither;B. Vukusic
最近的晶体学研究表明，TCR与肽/I类MHC复合物以单一的优选取向相互作用。尽管尚未对II类限制性TCR进行类似的研究，但已提出肽/II类复合物的T细胞识别具有类似的取向限制。本研究是对这一问题进行系统分析的一种功能方法。通过丙氨酸扫描诱变产生21种突变A β（d）分子，并评估其向一组具有有限TCR α和/或β链序列差异的牛胰岛素特异性T细胞杂交瘤呈递胰岛素物种变体的能力。我们证明，所有牛肉胰岛素特异性TCR在胰岛素/Ad复合物上具有相同的取向，使得α链与A β（d）α-螺旋的羧基末端区域相互作用，并且β链互补决定区3与肽的羧基末端部分相互作用，这与结晶TCR-肽/I类复合物所观察到的一致。尽管有这种结构限制，即使是具有结构相似性的TCR在其对该组MHC突变体的反应中也显示出显著的异质性。这种可变性似乎是由TCR与复合物结合诱导的构象变化和T细胞活化阈值的灵敏度引起的。
Recent crystallographic studies suggest that TCR interact with peptide/class I MHC complexes in a single preferred orientation. Although similar studies have not been performed for class II-restricted TCR, it has been proposed that T cell recognition of peptide/class II complexes has similar orientational restrictions. This study represents a functional approach to systematic analysis of this question. Twenty-one mutant A beta(d) molecules were produced by alanine scanning mutagenesis and assessed for their ability to present species variants of insulin to a panel of beef insulin-specific T cell hybridomas with limited TCR alpha- and/or beta-chain sequence differences. We demonstrate that all beef insulin-specific TCR have the same orientation on the insulin/Ad complex, such that the alpha-chain interacts with the carboxyl-terminal region of the A beta(d) alpha-helix, and the beta-chain complementarity-determining region 3 interacts with the carboxyl-terminal portion of the peptide, consistent with that observed for crystallized TCR-peptide/class I complexes. Despite this structural constraint, even TCR that share structural similarity show remarkable heterogeneity in their responses to the panel of MHC mutants. This variability appears to result from conformational changes induced by binding of the TCR to the complex and the exquisite sensitivity of the threshold for T cell activation.
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影响因子：
32.4
作者：
Scott, CA;Peterson, PA;Wilson, IA
通讯作者：
Wilson, IA
H2-Kb 限制性卵清蛋白肽的 TCR 识别方向的功能图谱表明，β 链亚基可以主导肽侧链特异性的确定。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Turner,SJ;Jameson,SC;Carbone,FR
通讯作者：
Carbone,FR
影响因子：
56.9
作者：
Garcia, KC;Degano, M;Wilson, IA
通讯作者：
Wilson, IA
T 细胞受体对其 MHC II 类：肽配体的定位。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hong,SC;Sant'Angelo,DB;Dittel,BN;Medzhitov,R;Yoon,ST;Waterbury,PG;JanewayJr,CA
通讯作者：
JanewayJr,CA
II 类基因表达的复杂调控：II 类突变细胞系的分析。
DOI：
--
发表时间：
1985
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Glimcher,LH;McKean,DJ;Choi,E;Seidman,JG
通讯作者：
Seidman,JG