Molecular characterization of the V gamma 9 T cell receptor repertoire expressed in patients with rheumatoid arthritis.

We have characterized the variable (V)gamma 9 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 V gamma 9 transcripts; gamma chain sequences were compared with those found in normal PBMC. For normal PBMC, a large proportion of V gamma 9 transcripts used the joining (J)gamma P gene segment whereas a few used J gamma 2. Despite this restriction in J gamma usage, there was extensive junctional region diversity with a unique sequence observed in each transcript examined. In contrast to normal PBMC, J gamma usage of V gamma 9 transcripts in PBMC of two patients was skewed towards J gamma 2. This deviation in J gamma usage was more pronounced in SMC since all patients expressed V gamma 9 transcripts in SMC which predominantly used J gamma 2, as opposed to J gamma P in normal PBMC. Further, approximately 60% of V gamma 9 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 V gamma 9-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 reflect in vivo expansion in response to a V gamma 9/J gamma 2 region-specific antigen. The data presented in this report suggest that V gamma 9+ T cells may play a role in the development of RA.