Differences in the reactivity of CD4+ T-cell lines generated against free versus nucleosome-bound SV40 large T antigen.

Previous results have revealed a strong correlation between polyomavirus BK reactivation and disease activity and antinuclear auto-antibody production in the human autoimmune disease systemic lupus erythematosus. BK virus establishes a latent infection in most humans, and reactivation requires the production of the DNA-binding large T antigen. Experimentally induced expression of the polyomavirus SV40 large T antigen in mice induces both an immune response to large T antigen and autoimmune response to nuclear antigens and antinuclear antibody production. Previous results have indicated that human T-antigen-specific CD4+ T-cell lines are stimulated equally by free, soluble and nucleosome-bound T antigen. This study was designed to determine how antigen processing of nucleosomes containing bound SV40 large T antigen may affect the specificity and response characteristics of experimentally induced T-antigen-specific CD4+ T cells. The results indicated that CD4+ T-cell lines generated from mice immunized with soluble, free T antigen responded very poorly in response to stimulation with T antigen bound to nucleosomes. CD4+ T-cell lines generated from mice immunized with nucleosomes that had bound T antigen in situ responded to both free and nucleosome-bound T antigen. The T-antigen-specific, CD4+ memory T cells induced by latent polyomavirus infections in humans may be uniquely suited to initiate autoimmunity to nuclear antigens upon virus reactivation.