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 study, we demonstrate that CD4-positive T cells from both normal and systemic lupus erythematosus (SLE) patients readily proliferate in response to pure T-antigen, and also to T-antigen in complex with nucleosomes. T-antigen-specific T cell lines from both normal individuals and SLE patients proliferate in response to nucleosome-T-antigen complexes, but not to nucleosomes or histones. B cells co-cultured with T-antigen-specific T cells and stimulated with nucleosome-T-antigen complexes produce anti-T-antigen and anti-DNA 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-antigen is actively expressed.
Andreassen
K
K
Department of Molecular Genetics Institute of Medical Biology, University of Tromso, Tromso, Norway.
Bredholt
G
G
Moens
U
U
Bendiksen
S
S
Kauric
G
G
Rekvig
O P
OP
D000328:Adult; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D005260:Female; D005434:Flow Cytometry; D006657:Histones / Q000276:immunology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D009707:Nucleosomes / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
D000974:Antibodies, Antinuclear; D000952:Antigens, Polyomavirus Transforming; D006657:Histones; D046911:Macromolecular Substances; D009707:Nucleosomes; D014316:Tritium; D013936:Thymidine