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 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.


CONCLUSIONS
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.
Andreassen
K
K
University Hospital of Tromsø, Norway.
Moens
U
U
Nossent
H
H
Marion
T N
TN
Rekvig
O P
OP
D000818:Animals; D017951:Antigen Presentation; D000957:Antigens, Viral, Tumor / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology*; D005260:Female; D006657:Histones / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D009707:Nucleosomes / Q000276:immunology* / Q000378:metabolism; D011120:Polyomavirus / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology*
D000957:Antigens, Viral, Tumor; D006657:Histones; D009707:Nucleosomes