The specificity of the interaction between the agretope of an antigen and an Ia-molecule can depend on the T cell clonotype.
The specificity of the interaction between the agretope of an antigen and an Ia-molecule can depend on the T cell clonotype.
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DOI：
10.1016/0161-5890(88)90096-x
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发表时间：
1988-07
影响因子：
3.6
通讯作者：
D. Plachov;H. Fischer;A. Reske-Kunz;E. Rüde
中科院分区：
文献类型：
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作者：
D. Plachov;H. Fischer;A. Reske-Kunz;E. Rüde
用分离的猪胰岛素A链免疫（B10 × B10.BR）F1小鼠，获得一系列T细胞克隆。T细胞克隆显示出相当大的多样性，这是由它们对猪、牛、羊和马胰岛素与相同的同源AbαAκβ分子组合的不同反应性所定义的。胰岛素的这些物种变体仅在所谓的A链环内的位置A8、A9或A10的氨基酸残基上彼此不同，并且小鼠对这些变体的应答性受Ir基因控制。对各种胰岛素/Ia组合的刺激能力的详细分析，包括抗Ia和L3 T4抗体的抑制实验，得出以下解释：氨基酸残基A8-A10参与胰岛素A链与Ia分子的相互作用。因此，这一地区可被视为协定的一部分。该区域内的结构变化可以改变胰岛素变体的刺激效力。然而，一个特定的氨基酸取代是否导致增强或减少的反应取决于所涉及的T细胞克隆的精细特异性。因此，Ia分子与抗原的相互作用不能单独解释抗原表位的功能特异性，而是这还取决于参与识别的特定T细胞受体的结构。
A series of T cell clones was developed from (B10 × B10.BR)F1 mice immunized with the isolated A chain of pig insulin. The T cell clones show considerable diversity as denned by their distinct reactivities to pig, beef, sheep and horse insulins in combination with the same syngeneic AbαAκβmolecules. These species variants of insulin differ from each other only in amino acid residues in position A8, A9 or A10 within the so-called A chain loop and responsiveness of mice to these variants is under Ir gene control. A detailed analysis of the stimulatory capacity of various insulin/Ia combinations including inhibition experiments with anti-Ia- and -L3T4 antibodies led to the following interpretation: the amino acid residues A8-A10 are involved in the interaction of the insulin A chain with the Ia molecules. This region can, therefore, be regarded as part of the agretope. Structural variations within this region can modify the stimulatory potency of the insulin variants. However, whether a particular amino acid substitution results in an enhancement or a reduction of the response depends on the fine specificity of the T cell clone involved. Thus, an interaction of la molecules with antigen cannot solely account for the functional specificity of an agretope, rather this also depends on the structure of the particular T cell receptor that participates in recognition.