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 s tudy, we demonstrate that CD4-positive T cells from both normal and systemi c lupus erythematosus (SLE) patients readily proliferate in response to pur e T-antigen, and also to T-antigen in complex with nucleosomes. T-antigen-s pecific T cell lines from both normal individuals and SLE patients' prolife rate in response to nucleosome-T-antigen complexes, but not to nucleosomes or histones. B cells co-cultured with T-antigen-specific T cells and stimul ated with nucleosome-T-antigen complexes produce anti-T-antigen and anti-DN A 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-anti gen is actively expressed.