PERSISTENCE OF DOMINANT T-CELL CLONES IN SYNOVIAL TISSUES DURING RHEUMATOID-ARTHRITIS

In a previous study, we showed that the T cell repertoire is biased in the synovial membrane (SM) compared with peripheral blood during rheu matoid arthritis (RA). The same bias was observed in different joints from the same patient and seems to be the same over time. To discover whether this bias was due to expansion of a clonal subset resulting fr om activation by conventional Ag(s) or to polyclonal stimulation by su perantigen(s), we sequenced more than 650 TCRBV-D-J junctional regions from freshly isolated SM and peripheral blood of two DR4-RA patients. From each patient, two SM were obtained on the same day, and a third was obtained later. Several dominant clones were found in SM but not i n peripheral blood. Some of them were found only at the first time poi nt in anatomically different SM, the majority persisted over time, and others were detected only at the second time point. Analysis of the c omplementarity-determining region 3 (CDR3) showed a bias in TCRBD and amino acid usage. Valine, encoded by randomly inserted N nucleotides, was used by 45% of dominant clones compared with 18% in the control po pulation (p < 0.001). In addition, GXXG and TSG moths were frequently observed in the CDR3 of these dominant clones. These data indicate a d ynamic TCR selection process during the perpetuation phase of RA. The dynamic changes of dominant clones also suggest a determinant spreadin g mechanism during RA.