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

Abstract

To investigate whether polyomavirus T antigen linked to histones through nucleosome-T antigen complexes has the potential to terminate histone-specific T cell anergy. 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. 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. 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.