HLA-B27-restricted cytotoxic T lymphocyte responses to arthritogenic enterobacteria or self-antigens are dominated by closely related TCRBV gene segments. A study in patients with reactive arthritis.
Identification of the T-cell receptors (TCR) used by synovial cytotoxic T lymphocytes (CTL) of patients with reactive arthritis (ReA) may be crucial to better understanding the pathogenetic mechanism underlying the HLA-B27 association of spondylarthropathies. The authors, therefore, sequenced 25 TCRB chains from HLA-B27-restricted CD8+ CTL clones and two clonal lines specific for self- or Yersinia enterocolitica antigen isolated from synovial fluids of 3 HLA-B27+ patients with ReA and PBL of one healthy HLA-B27+ individual. Fourteen non-HLA-B27-restricted CTL served as controls. Both autoreactive and Y. enterocolitica specific HLA-B27-restricted CTL used a highly limited set of VB genes with preferential rearrangement of three closely related VB families (VB 13, 14, 17), suggesting that these families contain a preferred site for contact with the HLA-B27 molecule. In addition, the presence of limited TCRBJ usage, limited heterogeneity in CDR3 sequences and dominant clones from individual donors among these CTL indicate that TCRB chain usage is further restricted by a limited set of peptides bound to the HLA-B27 molecule. Limited TCR usage by SF CTL of ReA patients may lay a basis for therapeutical manipulation of the T-cell response in the spondylarthropathies.
Duchmann
R
R
First Department of Medicine, Johannes Gutenberg University of Mainz, Germany.
May
E
E
Ackermann
B
B
Goergen
B
B
Meyer zum Büschenfelde
K H
KH
Märker-Hermann
E
E
D000328:Adult; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000276:immunology; D016918:Arthritis, Reactive / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002690:Chlamydia Infections / Q000276:immunology; D002692:Chlamydia trachomatis / Q000276:immunology; D004247:DNA / Q000032:analysis; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor / Q000235:genetics; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D000091402:Prohibitins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012480:Salmonella Infections / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology; D013582:Synovial Fluid / Q000276:immunology / Q000382:microbiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015009:Yersinia Infections / Q000276:immunology; D015008:Yersinia enterocolitica / Q000276:immunology* / Q000302:isolation & purification
D000942:Antigens, Bacterial; D001324:Autoantigens; D015796:HLA-B27 Antigen; C000717331:PHB2 protein, human; D000091402:Prohibitins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA