Lower receptor avidity required for thymic clonal deletion than for effector T-cell function

Hanspeter Pircher, Urs Hoffmann Rohrer, Dimitrios Moskofidis, Rolf M. Zinkernagel, Hans Hengartner

Research output: Contribution to journalArticle

251 Scopus citations

Abstract

CLONAL deletion in the thymus plays a major part in T-cell tolerance to self antigens1-3. But the mechanism of negative selection, its fine specificity and the threshold of affinity and avidity remains unknown. We have now examined these aspects of negative selection with mice expressing a transgenic T-cell receptor with specificity for lymphocytic choriomeningitis virus (LCMV) glycoprotein in association with the class I H-2Db molecule. These mice were rendered tolerant to LCMV by neonatal infection with mutant LCMVs hearing point mutations in the T-cell epitope recognized by the transgenic T-cell receptor (ref. 4). Variant LCMVs were also tested for their ability to elicit antiviral responses in transgenic mice in vivo and in vitro. Comparison in vivo revealed that a low-avidity receptor interaction, which was unable to induce effector T cells in the periphery, was still sufficient for clonal deletion in the thymus.

Original languageEnglish (US)
Pages (from-to)482-485
Number of pages4
JournalNature
Volume351
Issue number6326
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

ASJC Scopus subject areas

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