A physiological ligand of positive selection is seen with high specificity

Stefan Irion, Ranee E. Berg, Uwe D. Staerz

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Positive selection is a process that ensures that peripheral T cells express TCR that are restricted to self-MHC molecules. This process requires both self-MHC and self-peptides. We have recently established a TCR transgenic mouse model (C10.4 TCR(trans)+) in which the transgenic TCR was selected on the nonclassical MHC class Ib molecule H2-M3 in conjunction with a physiologically occurring peptide derived from the mitochondrial NADH- dehydrogenase subunit 1 gene (9-mer peptide). Here, the specificity of positive selection of C10.4 TCR(trans)+ T cells was examined using a fetal thymic organ culture system. We demonstrated that at low peptide concentrations, shortening the NADH-dehydrogenase subunit 1 gene 9-mer peptide or mutating its surface-exposed side chains severely impaired its ability to induce positive selection. We concluded that under physiological conditions positive selection of C10.4 TCR(trans)+ T cells was highly specific and occurred at low epitope densities.

Original languageEnglish
Pages (from-to)4601-4606
Number of pages6
JournalJournal of Immunology
Volume164
Issue number9
DOIs
StatePublished - 1 May 2000

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