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Dendritic cells process internalized antigens to present degradative products on MHC for TCR recognition. Because antigen-exposed DCs also induce humoral immunity, DCs must also retain antigen in its native state for the engagement of BCR on B cells. Here, we demonstrate that antigen endocytosed by the inhibitory Fc receptor, FcgammaRIIB, accesses a(More)
The pattern recognition receptor, RAGE, has been shown to be involved in adaptive immune responses but its role on the components of these responses is not well understood. We have studied the effects of a small molecule inhibitor of RAGE and the deletion of the receptor (RAGE-/- mice) on T cell responses involved in autoimmunity and allograft rejection.(More)
Receptor for advanced glycation end products (RAGE) is an activation receptor triggered by inflammatory S100/calgranulins and high mobility group box-1 ligands. We have investigated the importance of RAGE on Ag priming of T cells in murine models in vivo. RAGE is inducibly up-regulated during T cell activation. Transfer of RAGE-deficient OT II T cells into(More)
We have developed a model of autoimmunity to investigate autoantibody-mediated cross-presentation of self antigen. RIP-mOVA mice, expressing OVA in pancreatic beta cells, develop severe autoimmune diabetes when given OT-I cells (OVA-specific CD8(+) T cells) and anti-OVA IgG but not when given T cells alone. Anti-OVA IgG is not directly injurious to the(More)
Anti-DNA antibodies are a major contributor to the pathogenesis associated with the autoimmune disease systemic lupus erythematosus in mice and human. The accumulation of a large body of structural information on autoimmune anti-DNA antibodies over the past several years, particularly from mice, has provided considerable insight into the structure,(More)
Spontaneous anti-DNA antibodies in autoimmune mice have the characteristics of antibody produced by Ag-specific, clonally selective B cell stimulation. The nature of the somatically derived antibody V region structures recurrent among spontaneous anti-DNA antibodies suggests that DNA or DNA-protein complexes may provide the antigenic stimulus for autoimmune(More)
The uptake of immune complexes by FcRs on APCs augments humoral and cellular responses to exogenous Ag. In this study, CD11c+ dendritic cells are shown to be responsible in vivo for immune complex-triggered priming of T cells. We examine the consequence of Ab-mediated uptake of self Ag by dendritic cells in the rat insulin promoter-membrane OVA model and(More)
Spontaneous anti-DNA antibodies in autoimmune mice have the characteristics of antibodies produced by antigen-specific, clonally selective B cell stimulation. The nature of the somatically derived antibody variable region structures recurrent among spontaneous anti-DNA antibodies suggests that DNA or DNA-protein complexes may provide the antigenic stimulus(More)
Th cells recognize protein Ags as short peptides bound to MHC class II molecules. Altered peptide ligands can antagonize (inhibit) T cell responses to stimulatory peptides. Peptides generated by APC may contain peptide flanking residues (PFR), which lie outside the minimal binding epitope and can be recognized by the TCR. Our data show that PFR-dependent T(More)
Plasmacytoid dendritic cells (pDCs) are key regulators of the innate immune response, yet their direct role as APCs in the adaptive immune response is unclear. We found that unlike conventional DCs, immune complex (IC) exposed murine pDCs neither up-regulated costimulatory molecules nor activated Ag-specific CD4(+) and CD8(+) T cells. The inability of(More)