Oligoclonal T cells in rheumatoid arthritis: identification strategy and molecular characterization of a clonal T-cell receptor.
Immunodominant antigens in rheumatoid arthritis (RA) should induce an expansion of T cells bearing a corresponding T-cell receptor (TCR). We therefore analysed the TCR repertoire at the site of inflammation using two fundamentally different strategies. The total TCR repertoire was examined by generating 'representative' T-cell clone panels, which were subsequently tested for clonality by restriction mapping of the TCR beta gene locus. No clonality was detected in large T-cell clone panels generated with cells from three patients. However, when we selectively analysed the TCR repertoire of in vivo pre-activated, interleukin-2 (IL-2)-responsive T cells, significant T-cell/TCR clonality was found in 2 out of 4 patients. The clonal T cells represented a minority of the total T-cell population with an estimated frequency of 1 in 300 to 1 in 1000 cells. Molecular characterization of a clonal TCR and the use of a specific TCR V beta MoAb ruled out an over-representation of T cells bearing the same V beta element in the total T-cell population, rendering the involvement of super-antigens in the induction of T-cell clonality in this case unlikely.
Max-Planck-Society Research Unit for Rheumatology/Immunology, Institute for Clinical Immunology of the University, Erlangen, Germany.
U
U
Korthäuer
B
B
Hennerkes
H
H
Menninger
H W
HW
Mages
J
J
Zacher
A J
AJ
Potocnik
F
F
Emmrich
R A
RA
Kroczek
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D002999:Clone Cells; D003001:Cloning, Molecular; D005434:Flow Cytometry; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013582:Synovial Fluid / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta