Selective reduction of T cells bearing invariant Vα24JαQ antigen receptor in patients with systemic sclerosis

Abstract

A novel subset of T cells characterized by the expression of an invariant T cell antigen receptor (TCR) encoded by Vα24JαQ gene segments was investigated in patients with systemic sclerosis (SSc). Polymerase chain reaction analysis demonstrated that the Vα24 TCR repertoire was selectively used in CD4-CD8- double-negative T cells both in patients and in healthy individuals, while almost all families of TCRVα were expressed in single- positive T cell fractions. The Vα24+ double-negative T cells were increased by approximately fivefold in patients. However, sequence analysis clearly showed significant differences in the Vα24 TCR repertoire dominating in patients and healthy donors. In healthy individuals, the invariant Vα24JαQ was expanded and comprised 20-50% of the total TCR-α, while their selective reduction was observed in SSc patients who also showed expansion of invariant Vα24 TCR other than Vα24JαQ. Analogous to murine invariant Vα14Jα281 TCR, these results suggest that T cells with invariant Vα24JαQ TCR would function as regulatory T cells, whereas T cells bearing other invariant Vα24 TCR in SSc patients could be autoaggressive T cells in nature.