T cell autoimmunity to histones and nucleosomes is a latent property of the normal immune system.
OBJECTIVE
Investigators in this study undertook to determine whether in vitro antigen-responsive immune (polyomavirus T antigen [T-ag]- specific) and autoimmune (histone-specific) T cells from normal individuals share structural and genetic characteristics with those from patients with systemic lupus erythematosus (SLE).


METHODS
Histone-specific T cells were generated by stimulation of peripheral blood mononuclear cells (PBMCs) with nucleosome-T-ag complexes and were subsequently maintained by pure histones. T-ag-specific T cell clones were initiated and maintained by T-ag. The frequencies of circulating histone- and T-ag-specific T cells were determined in healthy individuals and in SLE patients by limiting dilution of PBMCs. T cell receptor (TCR) gene usage and variable-region structures were determined by complementary DNA sequencing. These sequences were compared between T-ag- and histone-specific T cells and between normal individuals and SLE patients for each specificity.


RESULTS
Individual in vitro-expanded histone- and T-ag-specific T cells from normal individuals displayed identical TCR V(alpha) and/or V(beta) chain third complementarity-determining region (CDR3) sequences, indicating that they were clonally expanded in vivo. The frequencies of in vitro antigen-responsive T-ag- or histone-specific T cells from normal individuals were similar to those from SLE patients. Although heterogeneous for variable-region structure and gene usage, histone-specific T cells from healthy individuals and SLE patients selected aspartic and/or glutamic acids at positions 99 and/or 100 of the V(beta) CDR3 sequence.


CONCLUSIONS
Autoimmune T cells from healthy individuals can be activated by nucleosome- T-ag complexes and maintained by histones in vitro. Such T cells possessed TCR structures similar to those from SLE patients, demonstrating that T cell autoimmunity to nucleosomes may be a latent property of the normal immune system.
Andreassen
Kristin
K
Department of Molecular Genetics, University of Tromsø, Tromsø, Norway.
Bendiksen
Signy
S
Kjeldsen
Elisabeth
E
Van Ghelue
Marijke
M
Moens
Ugo
U
Arnesen
Egil
E
Rekvig
Ole Petter
OP
D000328:Adult; D000596:Amino Acids / Q000235:genetics; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D003001:Cloning, Molecular; D022801:Complementarity Determining Regions / Q000235:genetics; D005260:Female; D006657:Histones / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D009707:Nucleosomes / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000596:Amino Acids; D001324:Autoantigens; D022801:Complementarity Determining Regions; D006657:Histones; D007135:Immunoglobulin Variable Region; D009707:Nucleosomes; D016693:Receptors, Antigen, T-Cell, alpha-beta