T cell lines specific for polyomavirus T-antigen recognize T-antigen complexed with nucleosomes: a molecular basis for anti-DNA antibody production.

We have previously demonstrated that in vivo expression of the polyomavirus DNA-binding T-antigen initiated production of IgG antibodies to T-antigen and to DNA, but not to a panel of autoantigens not related to nucleosomes, indicating an antigen-selective T cell-dependent B cell response. In this study, we demonstrate that CD4-positive T cells from both normal and systemic lupus erythematosus (SLE) patients readily proliferate in response to pure T-antigen, and also to T-antigen in complex with nucleosomes. T-antigen-specific T cell lines from both normal individuals and SLE patients proliferate in response to nucleosome-T-antigen complexes, but not to nucleosomes or histones. B cells co-cultured with T-antigen-specific T cells and stimulated with nucleosome-T-antigen complexes produce anti-T-antigen and anti-DNA antibodies, indicating that such CD4-positive T cells have the potential to interact with B cells specific for individual components of nucleosome-T-antigen complexes. Thus, a non-self DNA-binding protein like polyomavirus T-antigen may initiate and maintain an antibody response to DNA when T-antigen is actively expressed.