1. Rare, structurally homologous self-peptides promote thymocyte positive selection.
- Author
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Santori FR, Kieper WC, Brown SM, Lu Y, Neubert TA, Johnson KL, Naylor S, Vukmanović S, Hogquist KA, and Jameson SC
- Subjects
- Actin Depolymerizing Factors, Animals, Autoantigens chemistry, Biological Assay, Cell Differentiation, Cytoskeletal Proteins chemistry, Destrin, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microfilament Proteins chemistry, Peptides chemistry, Protein Conformation, Trans-Activators chemistry, Tumor Cells, Cultured, beta Catenin, Autoantigens immunology, Cytoskeletal Proteins immunology, Microfilament Proteins immunology, Peptides immunology, Receptors, Antigen, T-Cell immunology, Thymus Gland cytology, Trans-Activators immunology
- Abstract
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.
- Published
- 2002
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