“…Another observation that does not support random clonal expansion is that not all genes analyzed were found to be used by the expanded clonotypes, particularly BV5S1, as also noted by others (5,19), which is normally highly expressed and might account for 5-20% of total TCRBV expression (8,15,33). Moreover, the repeated observation of T cell clones expressing members of particular TCRBV gene families, such as BV1, BV2, BV3, BV6, BV8, and BV12, could be connected to the increased expression of several of these genes identified previously in the synovia of RA patients (2,(5)(6)(7). Clearly, functional in vitro studies with T cell clones and synovial antigens or synthetic peptide libraries will be required to characterize the specificity of the clonotypes expanded in the inflamed joints and to determine the nature of the stimulus.…”