Linked production of antibodies to mammalian DNA and to human polyomavirus large 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 polyomavirus replication, correlates with the presence of antibodies to single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), or the autologous TATA-binding protein (TBP).


METHODS
Sera from patients with various diagnosed or suspected autoimmune syndromes were analyzed for the presence of antibodies to T antigen, DNA, or TATA-binding protein, and correlations were determined. Rheumatoid factor (RF) was studied as a control antibody.


RESULTS
A highly significant correlation between antibodies to T antigen and antibodies to ssDNA or TATA-binding protein, but not between anti-T antigen antibodies and RF, was found in all patient groups. Of all sera that were positive for antibodies to dsDNA, 62% were positive for antibodies to T antigen (P<0.03).


CONCLUSIONS
A non-self DNA-binding protein such as human polyomavirus large T antigen may render DNA immunogenic upon binding to nucleosomes when expressed in vivo. This is indicated by the strong correlation between antibodies to T antigen and antibodies to DNA or TBP and is consistent with a hapten-carrier model. This model implies cognate antigen-selective interaction of T antigen-specific T helper cells and DNA-specific B cells or B cells specific for other components of nucleosomes, consistent with the results of previous experiments.
Bredholt
G
G
University of Tromsoe, Norway.
Olaussen
E
E
Moens
U
U
Rekvig
O P
OP
D000974:Antibodies, Antinuclear / Q000097:blood; D000917:Antibody Formation; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood; D001782:Blood Donors; D004247:DNA / Q000276:immunology*; D018983:DNA Footprinting; D004277:DNA, Single-Stranded / Q000276:immunology*; D003953:Diagnosis-Related Groups; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D012015:Reference Standards
D000974:Antibodies, Antinuclear; D000952:Antigens, Polyomavirus Transforming; D004277:DNA, Single-Stranded; D004247:DNA