Common intra-articular T cell expansions in patients with reactive arthritis: identical beta-chain junctional sequences and cytotoxicity toward HLA-B27.
Spondyloarthropathies constitute a group of autoimmune diseases of special interest because of their tight association with the MHC class I molecule HLA-B27 and the bacterial triggering of some clinical forms called reactive arthritis (ReA). One current hypothesis is the presentation by HLA-B27 of a so-called arthritogenic peptide to T cells. To better focus on the relevant T cell populations within the joint, we performed an extensive beta-chain T cell repertoire analysis of synovial fluid compared with PBL in seven patients, four of whom were characterized as having ReA triggered by Yersinia enterocolitica, Chlamydia trachomatis, or Shigella sonnei. Analysis of the size diversity of the beta-chain complementarity-determining region 3 (CDR3) allowed us to evaluate the degree of T cell clonality in the samples. Oligoclonal T cell expansions were frequently observed in the joint. In one patient, CDR3 amino acid sequences of major expansions using two different BV genes were identical. One dominant T cell expansion and several CDR3 amino acid sequences were identical in two different patients. Furthermore, one sequence was identical with a sequence reported independently in a Salmonella-induced ReA patient. Together, these data indicate a surprisingly high degree of conservation in the T cell responses in recent-onset ReA triggered by different micro-organisms. A CD8+ synovial line expressing shared clonotypes was established and reacted toward several B*2705 lymphoblastoid cell lines, therefore supporting a molecular mimicry phenomenon at the T cell level in the disease mechanism.
Dulphy
N
N
Laboratoire d'Immunologie et d'Histocompatibilité, Institut National de la Santé et de la Recherche Médicale, Unit 396, Université Paris VII, Centre G. Hayem, Hôpital Saint-Louis, Paris, France.
Peyrat
M A
MA
Tieng
V
V
Douay
C
C
Rabian
C
C
Tamouza
R
R
Laoussadi
S
S
Berenbaum
F
F
Chabot
A
A
Bonneville
M
M
Charron
D
D
Toubert
A
A
D000328:Adult; D000595:Amino Acid Sequence; D016918:Arthritis, Reactive / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D007719:Knee Joint / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008875:Middle Aged; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology; D000091402:Prohibitins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D013582:Synovial Fluid / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology*; D014407:Tumor Cells, Cultured
D015796:HLA-B27 Antigen; C000717331:PHB2 protein, human; D000091402:Prohibitins; D016693:Receptors, Antigen, T-Cell, alpha-beta