Molecular characterization of the Vγ9 T cell receptor repertoire expressed in patients with rheumatoid arthritis

摘要

AbstractWe have characterized the variable (V)γ9 T cell receptor (TcR) repertoire expressed in synovial membrane (SMC) and peripheral blood mononuclear cells (PBMC) of five rheumatoid arthritis (RA) patients. The experimental approach was to sequence the junctional regions of polymerase chain reaction (PCR)‐amplified Vγ9 transcripts; γ chain sequences were compared with those found in normal PBMC. For normal PBMC, a large proportion of Vγ9 transcripts used the joining (J)γP gene segment whereas a few used Jγ2. Despite this restriction in Jγ usage, there was extensive junctional region diversity with a unique sequence observed in each transcript examined. In contrast to normal PBMC, Jγ usage of Vγ9 transcripts in PBMC of two patients was skewed towards Jγ2. This deviation in Jγ usage was more pronounced in SMC since all patients expressed Vγ9 transcripts in SMC which predominantly used Jγ2, as opposed to JγP in normal PBMC. Further, approximately 60 of Vγ9 transcripts in PBMC of each of three patients had identical junctional region sequences, although the specific sequences were unique in each patient. For two of these patients the dominant transcript found in the PBMC was detected in the corresponding SMC at about 10 and 40, respectively. Overall, our findings indicate that Vγ9‐bearing T cells in RA peripheral blood are largely derived from clonal expansion whereas in the synovium there is expression of a population of these cells that are mainly polyclonal. This may reflectin vivoexpansion in response to a Vγ9/Jγ2 region‐specific antigen. The data presented in this report suggest that Vγ9+T cells may play a role