Sette A, Adorini L, Appella E, Colón S M, Miles C, Tanaka S, Ehrhardt C, Doria G, Nagy Z A, Buus S
Cytel, La Jolla, CA 92037.
J Immunol. 1989 Nov 15;143(10):3289-94.
We have analyzed the structural characteristics of the interaction between I-Ed molecules and their peptide ligands. It was found that unrelated good I-Ed binders share structurally similar "core" regions that were experimentally demonstrated to be crucial for binding to I-Ed molecules. Single amino acid substitution analogues of one good I-Ed binder, hen egg lysozyme 107-116, were analyzed for their capacity to bind to I-Ed molecules and to activate two different I-Ed-restricted T cell hybridomas. The results illustrate the great permissiveness of I-Ed-peptide interaction and the great specificity of T cell recognition. It was concluded from these analyses that basic residues on the peptide molecule play a crucial role in binding to I-Ed. This contrasts with the structural requirements for binding to the other Iad isotype, I-Ad, the crucial hydrophobic residues. Thus, different class II molecules of the same MHC haplotype may have rather distinct peptide binding specificities, thereby expanding the repertoire of possible immunogenic peptides presented for T cell recognition.
我们分析了I-Ed分子与其肽配体之间相互作用的结构特征。发现不相关的良好I-Ed结合物具有结构相似的“核心”区域，实验证明这些区域对于与I-Ed分子结合至关重要。对一种良好的I-Ed结合物——鸡蛋溶菌酶107-116的单氨基酸取代类似物进行了分析，以研究它们与I-Ed分子结合以及激活两种不同的I-Ed限制性T细胞杂交瘤的能力。结果说明了I-Ed-肽相互作用具有很大的宽容性以及T细胞识别具有很大的特异性。从这些分析中得出结论，肽分子上的碱性残基在与I-Ed结合中起关键作用。这与结合另一种Iad同种型I-Ad的结构要求形成对比，后者关键的是疏水残基。因此，同一MHC单倍型的不同II类分子可能具有相当不同的肽结合特异性，从而扩大了呈递给T细胞识别的可能免疫原性肽的库。
