Identification of T-cell epitopes on U1A protein in MRL/lpr mice: double-negative T cells are the major responsive cells

Systemic lupus erythematosus (SLE) is characterized by the existence of a heterogeneous group of autoantibodies such as anti-DNA, chromatin, histone, and ribonucleoprotein antibodies (Abs). Although the B-cell antigenic determinants have been well characterized, very limited data about the T-cell epitopes of self-antigen (Ag) have been reported. In the present study, we analysed auto-T-cell epitopes using bone marrow-derived dendritic cells (BM-DCs) pulsed with murine U1A (mU1A) protein capable of activating autoreactive T cells from unprimed MRL/lpr mice in vitro. The data suggested that there are at least four T-cell epitopes on the U1A protein, U1A(31-50), U1A(61-80), U1A(201-220) and U1A(271-287), and U1A(31-50) had the most significant T-cell proliferative response. In addition, the main responsive T cells are the CD4(-) CD8(-) double-negative subgroup of T cells. Furthermore, we also demonstrated that the activation of double-negative T cells is major histocompatibility complex class II restricted. The study here provides information on T-cell epitope analysis of the U1A antigen using BM-DCs as the effective antigen-presenting cells.