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

Immunity. 1995 Jun;2(6):597-605. doi: 10.1016/1074-7613(95)90004-7.


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 04-associated disease. By comparing frequencies of V beta-J beta combinations, healthy individuals segregated into independent clusters, which strongly correlated with the HLA-DRB1 allele expression. The repertoire fingerprint imposed by the HLA-DRB1 alleles involved only a selected group of J beta elements, whereas the distribution of the other J beta segments was HLA independent. The HLA-restricted J beta elements are characterized by a Gly-Pro-Gly sequence within the conserved Phe-Gly-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / metabolism*
  • Base Sequence
  • Cluster Analysis
  • HLA-DR Antigens / genetics
  • Humans
  • Molecular Sequence Data
  • Nucleic Acid Hybridization
  • Polymerase Chain Reaction
  • Polymorphism, Genetic / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology


  • HLA-DR Antigens
  • Receptors, Antigen, T-Cell, alpha-beta