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

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Abstract
Objective To investigate whether polyomavirus T antigen linked to histones through nucleosome–T antigen complexes has the potential to terminate histone‐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, histones, nucleosome–T antigen complexes, or nucleosomes. Proliferative responses of these lines to T antigen, histones, and nucleosomes were determined. Results Whereas T cell lines could be established using T antigen or T antigen–nucleosome complexes, histones or nucleosomes did not have this potential. However, T cell lines selected by T antigen–nucleosome complexes responded subsequently to histones and nucleosomes. Identical results were obtained with murine and human nucleosomes, provided that they were complexed with 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–specific T cells offer bystander help that may terminate histone‐specific T cell anergy. These T cells may progress into functional, autoimmune T cells if histones are properly presented.