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 est ablishes a latent infection in most humans, and reactivation requires the p roduction of the DNA-binding large T antigen. Experimentally induced expres sion of the polyomavirus SV40 large T antigen in mice induces both an immun e response to large T antigen and autoimmune response to nuclear antigens a nd antinuclear antibody production, Previous results have indicated that hu man T-antigen-specific CD4(+) T-cell lines are stimulated equally by free, soluble and nucleosome-bound T antigen. This study was designed to determin e how antigen processing of nucleosomes containing bound SV40 large T antig en may affect the specificity and response characteristics of experimentall y 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 n ucleosomes. CD4(+) T-cell lines generated from mice immunized with nucleoso mes 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 l atent polyomavirus infections in humans may be uniquely suited to initiate autoimmunity to nuclear antigens upon virus reactivation.