Mechanisms underlying the formation of the T cell receptor repertoire in rheumatoid arthritis

Debby R. Walser-Kuntz, Cornelia M. Weyand, Arthur J. Weaver, William M. O'fallon, Jörg J. Goronzy

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

The contributions of germline-encoded T cell receptor segments and of HLA-DR polymorphisms in shaping the repertoire of human CD4+ CD45RO- T cells were investigated in healthy unrelated Individuals and in patients with rheumatoid arthritis, an HLA-DRB1 *04associated disease. By comparing frequencies of Vβ-Jβ combinations, healthy Individuals segregated into independent clusters, which strongly correlated with the HLA-DRB1 allele expression. The repertoire finger-print imposed by the HLA-DRB1 alleles involved only a selected group of Jβ elements, whereas the distribution of the other Jβ segments was HLA Independent. The HLA-restricted Jβ elements are characterized by a Gly-Pro-Gly sequence within the conserved PheGly-X-Gly motif, which induces rigidity in an otherwise more flexible protein backbone. The T cell receptor repertoire distinguished patients with RA from healthy HLA-DR-matched individuals, suggesting that patients share a selection mechanism that significantly distorts the composition of the T cell receptor repertoire.

Original languageEnglish (US)
Pages (from-to)597-605
Number of pages9
JournalImmunity
Volume2
Issue number6
DOIs
StatePublished - Jun 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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