Immunity. 2002 Aug;17(2):131-42.

Rare, structurally homologous self-peptides promote thymocyte positive selection.

Santori FR, Kieper WC, Brown SM, Lu Y, Neubert TA, Johnson KL, Naylor S, Vukmanović S, Hogquist KA, Jameson SC.

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Michael Heidelberger Division of Immunology, Department of Pathology and Kaplan Cancer Center, New York University School of Medicine, 550 First Avenue, NY 10016, USA.

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.

PMID:: 12196285; [PubMed - indexed for MEDLINE]

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