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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adult, Amino Acids, Autoantigens, Autoimmunity, Cell Line, Cloning, Molecular, Complementarity Determining Regions, Female, Histones, Humans, Immune System, Immunoglobulin Variable Region, In Vitro Techniques, Lupus Erythematosus, Systemic, Middle Aged, Nucleosomes, Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes.
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Is t cell autoimmunity to histones and nucleosomes a latent property of the normal immune system? Context: 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). 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. 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.
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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. Final Decision: yes