Linked production of antibodies to mammalian DNA and to human polyomaviruslarge T antigen - Footprints of a common molecular and cellular process?

Objective, To test whether the presence of antibodies to human polyomavirus large T antigen, a viral DNA-binding protein essential for productive poly omavirus replication, correlates with the presence of antibodies to single- stranded DNA (ssDNA), double-stranded DNA (dsDNA), or the autologous TATA-b inding protein (TBP), Methods. Sera from patients with various diagnosed or suspected autoimmune syndromes were analyzed for the presence of antibodies to T antigen, DNA, o r TATA-binding protein, and correlations were determined. Rheumatoid factor (RIF) was studied as a control antibody. Results. A highly significant correlation between antibodies to T antigen a nd antibodies to ssDNA or TATA-binding protein, but not between anti-T anti gen antibodies and RF, was found in all patient groups. Of all sera that we re positive for antibodies to dsDNA, 62% were positive for antibodies to T antigen (P < 0.03). Conclusion, A non-self DNA-binding protein such as human polyomavirus large T antigen may render DNA immunogenic upon binding to nucleosomes when expr essed in vivo. This is indicated by the strong correlation between antibodi es to T antigen and antibodies to DNA or TBP and is consistent with a hapte n-carrier model. This model implies cognate antigen-selective interaction o f T antigen-specific T helper cells and DNA-specific B cells or B cells spe cific for other components of nucleosomes, consistent with the results of p revious experiments.