Characterization of self-T-cell response and antigenic determinants of U1A protein with bone marrow-derived dendritic cells in NZB x NZW F1 mice.

Systemic lupus erythematosus (SLE) is characterized by the existence of a heterogeneous group of autoantibodies directed against nuclear intact structures, such as nucleosomes and small nuclear ribonucleoproteins (snRNPs). Autoantibodies against snRNPs are of special interest because they are detectable in the majority of SLE patients. Although the B-cell antigenic determinants have been well characterized, very limited data have been reported in regard to the T-cell epitopes of snRNPs. Furthermore, several studies have demonstrated that determination of the auto-T-cell epitopes recognized by freshly isolated T cells is difficult from unprimed lupus mice when self-antigen-pulsed B cells or macrophages are used as antigen-presenting cells (APCs) in vitro. In the present study, we showed a novel approach for determining the auto-T-cell epitopes, using bone marrow-derived dendritic cells (BMDCs) pulsed with the murine U1A protein - an immunodominant antigen of the U1 snRNPs - which is capable of activating freshly isolated T cells from unprimed (NZB x NZW) F1 (BWF1) mice in vitro. The T-cell epitope area was found to be located at the C-terminus of U1A, overlapping the T-cell epitope of human U1A that has been reported in human SLE. Identification of the autoreactive T-cell epitope(s) in snRNPs will help to elucidate how reciprocal T-B determinant spreading of snRNPs emerges in lupus. The results presented here also indicate that it is feasible to use this approach to further explore strategies to design immunotherapy for patients with lupus.