We investigated the role of T cell receptor (TCR) V alpha 24+ T cells in the pathogenesis of systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The invariant V alpha 24 J alpha Q was expanded and comprised 50-90% of the total V alpha 24 in healthy individuals. In contrast, patients with SSc and SLE showed the selective reduction of the invariant V alpha 24 J alpha Q with oligoclonal expansion of V alpha 24 TCR other than V alpha 24 J alpha Q. Because human V alpha 24 J alpha Q TCR is analogous to murine invariant V alpha 14 J alpha 281 TCR which is the major genotype of NK T cells, these results suggest that the selective reduction of T cells with invariant V alpha 24 J alpha Q TCR might play an important role of the generation of autoreactive T cells including T cells bearing other V alpha 24 TCR in autoimmune disease patients.