The frequency of high avidity T cells determines the hierarchy of determinant spreading

J. Tian, S. Gregori, L. Adorini, D. L. Kaufman

Research output: Contribution to journalArticlepeer-review

Abstract

Autoimmunity often spreads in a predefined pattern during the progression of T cell-mediated autoimmune diseases. This progression has been well described in animal models and in man, but the basis for this phenomenon is little understood. To gain insight into the factors that determine this spreading hierarchy, we characterized the binding affinity of a panel of β cell-autoantigenic peptides to I-Ag7, as well as the precursor frequency, functional avidity, and phenotype of the T cells that recognize these peptides in type 1 diabetes-prone nonobese diabetic mice. We observed that autoimmunity gradually spreads from a β cell determinant, which had the largest precursor pool of high avidity T cells, to β cell determinants with progressively smaller and lower avidity T cell precursor pools. This correlation between the sequential development of spontaneous T cell autoimmunity and the frequency and avidity of autoantigen-reactive T cells suggests that the extent to which T cells were negatively selected by the self-determinants is the key factor determining the spreading hierarchy.

Original languageEnglish
Pages (from-to)7144-7150
Number of pages7
JournalJournal of Immunology
Volume166
Issue number12
Publication statusPublished - Jun 15 2001

ASJC Scopus subject areas

  • Immunology

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