Naturally processed chromatin peptides reveal a major autoepitope that primes pathogenic T and B cells of lupus.

Pathogenic T and B Cells of Lupus Reveal a Major Autoepitope That Primes Naturally Processed Chromatin Peptides

Low-dose peptide tolerance therapy of lupus generates plasmacytoid dendritic cells that cause expansion of autoantigen-specific regulatory T cells and contraction of inflammatory Th17 cells.

Subnanomolar doses of an unaltered, naturally occurring nucleosomal histone peptide epitope, H4(71-94), when injected s.c. into lupus-prone mice, markedly prolong lifespan by generating CD4+25+ and CD8+ regulatory T cells (Treg) producing TGF-beta. The induced Treg cells suppress nuclear autoantigen-specific Th and B cells and block renal inflammation. Splenic dendritic cells (DC) captured the ...

Phosphorylated Peptides Are Naturally Processed and Presented by Major Histocompatibility Complex Class I Molecules in Vivo

Posttranslational modification of peptide antigens has been shown to alter the ability of T cells to recognize major histocompatibility complex (MHC) class I-restricted peptides. However, the existence and origin of naturally processed phosphorylated peptides presented by MHC class I molecules have not been explored. By using mass spectrometry, significant numbers of naturally processed phospho...

Promiscuous Presentation and Recognition of Nucleosomal Autoepitopes in Lupus: Role of Autoimmune TCell Receptor a Chain

T cells specific for nucleosomal autoepitopes are selectively expanded in lupus mice and these Th cells drive autoimmune B cells to produce pathogenic antinuclear antibodies. We transfected the TCRa and b chain genes of a representative, pathogenic autoantibody-inducing Th clone specific for the nucleosomal core histone peptide H4 71–94 into TCR-negative recipient cells. Although the autoimmune...

Promiscuous Presentation and Recognition of Nucleosomal Autoepitopes in Lupus: Role of Autoimmune T Cell Receptor α Chain

T cells specific for nucleosomal autoepitopes are selectively expanded in lupus mice and these Th cells drive autoimmune B cells to produce pathogenic antinuclear antibodies. We transfected the TCR-alpha and -beta chain genes of a representative, pathogenic autoantibody-inducing Th clone specific for the nucleosomal core histone peptide H471-94 into TCR-negative recipient cells. Although the au...