Termination of human T cell tolerance to histones by presentation of histones and polyomavirus T antigen provided that T antigen is complexed with nucleosomes

Objective. To investigate whether polyomavirus T antigen linked to histones through nucleosome-T antigen complexes has the potential to terminate hist one-specific T cell anergy. Methods. Blood mononuclear cells from healthy individuals were used as the source to establish T cell lines initiated and maintained by T antigen, his tones, nucleosome-T antigen complexes, or nucleosomes. Proliferative respon ses of these lines to T antigen, histones, and nucleosomes were determined. Results. Whereas T cell lines could be established using T antigen or T ant igen-nucleosome complexes, histones or nucleosomes did not have this potent ial. However, T cell lines selected by T antigen-nucleosome complexes respo nded subsequently to histones and nucleosomes, Identical results were obtai ned with murine and human nucleosomes, provided that they were complexed wi th T antigen. Conclusion. T antigen-specific T cells possess the potential to proliferate when interacting with an antigen-presenting cell that presents T antigen. In the presence of T antigens complexed with nucleosomes, T antigen-specifi c T cells offer bystander help that may terminate histone-specific T cell a nergy, These T cells may progress into functional, autoimmune T cells if hi stones are properly presented.