Rheumatoid arthritis is associated with several human leukocyte antigen DRB1 types that express a common five-amino acid sequence called the shared epitope. Here we show that the human leukocyte antigen DRB1 shared epitope expands naive T lymphocytes that express the same T-cell-receptor variable region-joining region combinations that are prevalent in the synovia of rheumatoid arthritis patients. Thus, the shared epitope could affect rheumatoid arthritis disease susceptibility by selecting in the premorbid state specific T-cell subsets that contribute to synovial inflammation.