Santori Fabio R, Kieper William C, Brown Stuart M, Lu Yun, Neubert Thomas A, Johnson Kenneth L, Naylor Stephen, Vukmanović Stanislav, Hogquist Kristin A, Jameson Stephen C
Michael Heidelberger Division of Immunology, Department of Pathology and Kaplan Cancer Center, New York University School of Medicine, 550 First Avenue, NY 10016, USA.
Immunity. 2002 Aug;17(2):131-42. doi: 10.1016/s1074-7613(02)00361-8.
Although it is clear that positive selection of T cells involves recognition of specific self-peptide/MHC complexes, the nature of these self-ligands and their relationship to the cognate antigen are controversial. Here we used two complementary strategies to identify naturally occurring self-peptides able to induce positive selection of T cells bearing a specific T cell receptor, OT-I. Both the bioassay- and bioinformatics-based strategies identified the same self-peptides, derived from F-actin capping protein and beta-catenin. These peptides displayed charge conservation at two key TCR contact residues. The biological activity of 43 other self-peptides and of complex peptide libraries directly correlated to the extent of conservation at TCR contact residues. These results demonstrate that selecting self-peptides are rare and can be identified by homology-based search strategies.
虽然很明显T细胞的阳性选择涉及对特定自身肽/MHC复合物的识别，但这些自身配体的性质及其与同源抗原的关系仍存在争议。在这里，我们使用了两种互补策略来鉴定能够诱导携带特定T细胞受体OT-I的T细胞进行阳性选择的天然存在的自身肽。基于生物测定和生物信息学的策略都鉴定出了相同的自身肽，它们来源于F-肌动蛋白封端蛋白和β-连环蛋白。这些肽在两个关键的TCR接触残基处表现出电荷保守性。其他43种自身肽和复合肽文库的生物学活性与TCR接触残基处的保守程度直接相关。这些结果表明，具有选择作用的自身肽很少见，并且可以通过基于同源性的搜索策略来鉴定。
