STRUCTURAL-ANALYSIS OF TCR-LIGAND INTERACTIONS STUDIED ON H-2K(D)-RESTRICTED CLONED CTL SPECIFIC FOR A PHOTOREACTIVE PEPTIDE DERIVATIVE
STRUCTURAL-ANALYSIS OF TCR-LIGAND INTERACTIONS STUDIED ON H-2K(D)-RESTRICTED CLONED CTL SPECIFIC FOR A PHOTOREACTIVE PEPTIDE DERIVATIVE
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DOI：
10.1016/1074-7613(95)90158-2
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发表时间：
1995-07-01
期刊：
影响因子：
32.4
通讯作者：
ROMERO, P
中科院分区：
文献类型：
--
作者：
LUESCHER, IF;ANJUERE, F;ROMERO, P
为了研究T细胞受体（TCR）与其配体（即主要组织相容性复合体（MHC）分子和抗原肽的复合物）之间的相互作用，我们用具有光反应性的4 - 叠氮苯甲酸修饰了一种H - 2K（d）限制性抗原肽的一个TCR接触残基。光反应基团是由用这种肽衍生物免疫的小鼠所产生的细胞毒性T淋巴细胞（CTL）克隆所识别的表位的关键组成部分。这些克隆中的大多数表达由Vβ1编码的β链，其与由Jα TA28编码的α链配对。对于其中一种TCR，光亲和标记位点在α链上被定位为一个由Jα TA28编码的色氨酸，在β链上被定位为Vβ1的C'链的一个残基。这种TCR的分子模型表明存在一个疏水口袋，该口袋容纳这个色氨酸以及Vβ1的C'链上的一个酪氨酸，光反应性侧链插入在它们之间。结论是，这种亲和结合原理可能解释了对由Vβ1和Jα TA28编码的TCR的优先选择。
To study the interaction of the TCR with its ligand, the complex of a MHC molecule and an antigenic peptide, we modified a TCR contact residue of a H-2K(d)-restricted antigenic peptide with photoreactive 4-azidabenzoic acid. The photoreactive group was a critical component of the epitope recognized by CTL clones derived from mice immunized with such a peptide derivative. The majority of these clones expressed V beta 1-encoded beta chains that were paired with J alpha TA28-encoded a chains. For one of these TCR, the photoaffinity labeled sites were mapped on the a chain as a J alpha TA28-encoded tryptophan and on the beta chain as a residue of the C' strand of V beta 1. Molecular modeling of this TCR suggested the presence of a hydrophobic pocket that harbors this tryptophan as well as a tyrosine on the C' strand of V beta 1 between which the photoreactive side chain inserts. It is concluded that this avid binding principle may account for the preferential selection of V beta 1 and J alpha TA28-encoded TCR.