Distinct molecular mechanisms account for the specificity of two different T-cell receptors
Distinct molecular mechanisms account for the specificity of two different T-cell receptors
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DOI：
10.1021/bi026864
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发表时间：
2003-04-29
期刊：
影响因子：
2.9
通讯作者：
Sykulev, Y
中科院分区：
文献类型：
--
作者：
Anikeeva, N;Lebedeva, T;Sykulev, Y
对D3T细胞受体(TCR)与其天然配体(与人类白细胞抗原A*0201(HLA-A2)主要组织相容性复合体(MHC)蛋白结合的HIV多肽)相互作用的热力学分析表明，与2134 TCR与其多肽-MHC配体的结合既有相似之处，又有显著的差异。两个反应的平衡热力学参数与TCR-多肽-MHC复合物形成过程中结合界面的构象调整相一致。然而，使蛋白质表面脱水的渗透试剂对两个反应的强度的影响截然不同，表明水分子做出了非常不同的贡献--增强了D3TCR的结合，但削弱了2134TCR的结合。TCR使用这些不同的机制来识别配体可能是增强其固有交叉反应性的重要手段。
Analysis of the thermodynamics of the interactions between the D3 T-cell receptor (TCR) and its natural ligand, an HIV peptide bound to a HLA-A*0201 (HLA-A2) major histocompatibility complex (MHC) protein, shows both similarities and striking differences when compared with the 2134 TCR binding to its peptide-MHC ligand. The equilibrium thermodynamic parameters of both reactions are consistent with a conformational adjustment at the binding interface during the formation of specific TCR-peptide-MHC complexes. However, osmolytic reagents that dehydrate protein surfaces have profoundly different effects on the strength of the two reactions, indicating that water molecules make very different contributions-enhancing the binding of D3 TCR but weakening the binding of 2134 TCR. The use of these different mechanisms by TCRs to recognize ligands might be an important means augmenting their inherent cross-reactivity.