V alpha gene usage in rheumatoid compared with osteoarthritic synovial tissue T cells.
While many investigators have examined V gene usage by the clonotypic T-cell receptor (TCR) in rheumatoid arthritis (RA) joints, few have reported on arthritic controls. We compared TCR alpha-chain V gene usage in knee synovial tissue specimens from 9 RA and 5 osteoarthritis (OA) patients. There was no significant difference in the number of V gene families used in RA compared with OA synovium. However, there was an increased prevalence of V alpha 28, V alpha 10, V alpha 17, and V alpha 18 and under representation of V alpha 15 in RA compared with OA synovium. Of these, V alpha 28 was also recently described by us as being present in RA synovial tissue early in the course of disease. V alpha 28 associated J region usage, and N-regional diversity was surveyed in T-cell receptors from additional rheumatoid synovial tissue T-cell populations and normal peripheral blood. Oligoclonality was observed in 6/10 rheumatoid specimens either by direct sequencing or where three or more molecular clones were sequenced, compared with 0/5 normal PBMCs. The oligoclonal populations included 2/3 cell lines stimulated with interleukin-2 (IL-2) alone. Several novel J regions were observed, with some recurrent residues observed at N-region positions. These data indicate an increased prevalence of certain TCR V region families in RA versus OA synovium, and suggest an antigen-driven expansion of V alpha 28-expressing T cells in RA synovium.
Zwillich
S H
SH
Department of Medicine, Clinical Immunology/Rheumatology Unit, University of Rochester Medical Center, NY 14642.
Fang
Q
Q
Kieber-Emmons
T
T
Vonfeldt
J
J
Monos
D
D
Ramanujam
T
T
Wang
B
B
Weiner
D B
DB
Willams
W V
WV
D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D018740:Genetic Heterogeneity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000276:immunology*; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013582:Synovial Fluid / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
D017931:DNA Primers; D016693:Receptors, Antigen, T-Cell, alpha-beta; C089747:T cell receptor Valpha28