Brock R, Wiesmüller K H, Jung G, Walden P
Max-Planck-Institut für Biologie, Abteilung Immungenetik, Tübingen, Germany.
Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13108-13. doi: 10.1073/pnas.93.23.13108.
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-2Ld and an endogenous octapeptide, and of the self-MHC molecule H-2Kb 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.
2C是一个典型的同种异体反应性细胞毒性T淋巴细胞克隆，可识别两种不同的配体。这些配体是同种主要组织相容性复合体（MHC）分子H-2Ld与一种内源性八肽的加合物，以及自身MHC分子H-2Kb与另一种肽的加合物。采用合成肽结合分子建模研究的MHC结合和T细胞检测方法，分析这种交叉反应性的结构基础。两种复合物的分子表面在正负电荷的密度和分布上有很大差异。然而，增加相似性的肽修饰会降低所得MHC肽复合物诱导T细胞反应的能力。此外，肽在配体识别中的作用对于自身MHC限制和同种异体MHC限制的T细胞反应是不同的。自身MHC限制的T细胞反应对肽的识别进行了精细调节。另一方面，同种异体MHC限制的反应在很大程度上忽略了肽的修饰。结果强烈表明，T细胞受体对不同配体结构的适应性，而非配体的分子模拟，是2C交叉反应性的基础。这一结论对T细胞免疫学和免疫紊乱的理解具有重要意义。
