Selection ofhprtMutant T Cells as Surrogates for Dividing Cells Reveals a Restricted T Cell Receptor BV Repertoire in Insulin-Dependent Diabetes Mellitus

Abstract T cells with somatically acquired mutations in the hypoxanthine–guanine phosphoribosyltransferase ( hprt ) gene were isolated from patients with insulin-dependent diabetes mellitus (IDDM) as representatives of populations potentially enriched for in vivo activated T cells. TCRB gene V region usage among mutant isolates from individual IDDM patients, but not from normal controls, showed a pronounced preference for BV14 and, to a lesser extent, BV6. Wild-type (nonmutant) isolates did not show such preferences. Extensive in vivo clonal expansions of the BV14 expressing mutant T cells from IDDM patients were revealed by sequence identity of TCRB chain junctional regions. These data support restricted TCRB gene usage in T cell populations enriched for in vivo activated clones in patients with IDDM.