Molecular basis for the recognition of two structurally different major histocompatibility complex peptide complexes by a single T-cell receptor
Molecular basis for the recognition of two structurally different major histocompatibility complex peptide complexes by a single T-cell receptor
复制标题
DOI：
10.1073/pnas.93.23.13108
复制
发表时间：
1996-11-12
影响因子：
11.1
通讯作者：
Walden, P
中科院分区：
文献类型：
--
作者：
Brock, R;Wiesmuller, KH;Walden, P
2C是一种典型的同种异体反应性细胞毒性T淋巴细胞克隆，它识别两种不同的配体，这些配体是同种异体主要组织相容性复合物（MHC）分子H-2L（d）和内源性八肽的加合物，以及自身MHC分子H-2K（B）和另一种肽的加合物，MHC结合和T-使用合成肽的细胞测定结合分子模拟研究来分析这种交叉反应性的结构基础。这两种复合物的分子表面在正电荷和负电荷的密度和分布上有很大的不同，然而，增加相似性的肽的修饰降低了所得MHC肽复合物诱导T细胞应答的能力。此外，肽在配体识别中的作用对于自身和同种异体MHC限制性T细胞应答是不同的，自身MHC限制性T细胞应答被精细地调整以识别肽。另一方面，同种异体MHC限制性应答在很大程度上忽略肽的修饰。结果表明，T细胞受体对不同配体结构的适应，而不是配体的分子模拟，是2C交叉反应性的基础。这一结论对T细胞免疫学和免疫疾病的理解具有重要意义。
2C is a typical alloreactive cytotoxic T lymphocyte clone that recognizes two different ligands, These ligands are adducts of the allo-major histocompatibility complex (MHC) molecule H-2L(d) and an endogenous octapeptide, and of the self-MHC molecule H-2K(b) and another peptide, MHC-binding and T-cell assays with synthetic peptides in combination with molecular modeling studies were employed to analyze the structural basis for this crossreactivity. The molecular surfaces of the two complexes differ greatly in densities and distributions of positive and negative charges, However, modifications of the peptides that increase similarity decrease the capacities of the resulting MHC peptide complexes to induce T-cell responses, Moreover, the roles of the peptides in ligand recognition are different for self- and allo-MHC-restricted T-cell responses, The self-MHC-restricted T-cell responses were finely tuned to recognition of the peptide, The allo-MHC-restricted responses, on the other hand, largely ignore modifications of the peptide. The results strongly suggest that adaptation of the T-cell receptor to the different ligand structures, rather than molecular mimicry by the ligands, is the basis for the crossreactivity of 2C, This conclusion has important implications for T-cell immunology and for the understanding of immunological disorders.