S Ul-lfuTlary A novel subset ofT ceils characterized by the expression of an invariant T cell antigen receptor (TC1L) encoded by V0t24J~xQ gene segments was investigated in patients with systemic sclerosis (SSc). Polymerase chain reaction analysis demonstrated that the Vot24 TClL repertoire was selectively used in CD4-CD8-double-negative T cells both in patients and in healthy individuals, while almost all families of TCR.Vot were expressed in single-positive T cell fractions. The Vor + double-negative T cells were increased by approximately fivefold in patients. However, sequence analysis clearly showed significant differences in the Vo~24 TC1L repertoire dominating in patients and healthy donors. In healthy individuals, the invariant Vot24JoLQ was expanded and comprised 20-50% of the total TCR-ot, while their selective reduction was observed in SSc patients who also showed expansion of invariant Vex24 TCR other than Vot24JcxQ. Analogous to murine invariant V~14JoL281 TC1L, these results suggest that T cells with invariant V&24JotQ TCR would function as regulatory T cells, whereas T cells bearing other invariant Vex24 TCR in SSc patients could be autoaggressive T cells in nature. Recent studies by Porcelli et al. (6) and Dellabona et al. (7,8) indicate that the invariant Vcx24J~xQ sequence is preferentially expressed on DN ot/]3 T cells from healthy individuals. The homology of the nucleotide sequences is found to be 75% in the V0t24 and 90% in the CDR3 regions compared with murine Vo~24 TCR (9). Therefore, the human V&24 sequence is a homologue of murine V&14 TCP,. Another striking similarity to murine invariant V~14 T cells is that human peripheral DN T cells also express a limited TCR.-[3 repertoire including V [32, V[38, VI311,10). Interestingly, the decrease in invariant Vod4Jo~281 TCR expression in autoimmune prone mice correlates with disease development. It is thus likely that Vot14 § NK T cells play a role in the regulation ofautoimmune disease development.