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T cells from induced and spontaneous models of SLE recognize a common T cell epitope on β2-glycoprotein I.

T cells from induced and spontaneous models of SLE recognize a common T cell epitope on β2-glycoprotein I.
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Salem D, Subang R, Kuwana M, Levine JS, Rauch J,


Salem D, Subang R, Kuwana M, Levine JS, Rauch J, (click to view)

Salem D, Subang R, Kuwana M, Levine JS, Rauch J,

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Cellular & molecular immunology 2018 03 23() doi 10.1038/s41423-018-0013-3

Abstract

Systemic lupus erythematosus is a prototypic model for B-cell epitope spread in autoimmunity. Autoantibodies to numerous molecularly distinct self-antigens emerge in a sequential manner over several years, leading to disease manifestations. Among the earliest autoantibodies to appear are those targeting phospholipid-binding proteins, particularly β2-glycoprotein I. Notably, mice immunized with β2-glycoprotein I and lipopolysaccharide develop a strong T cell response to β2-glycoprotein I that is associated with autoantibody production and renal disease, similar to that seen in human SLE. Here we hypothesized that mice with murine systemic lupus erythematosus, whether induced or spontaneous, should have T cells that recognize β2-glycoprotein I. We evaluated the response of splenic T cells from mice with induced (C57BL/6 and C3H/HeN) and spontaneous (MRL/lpr) systemic lupus erythematosus to peptides spanning the entire sequence of human β2GPI. We found that mice with induced and spontaneous systemic lupus erythematosus recognize a common T cell epitope (peptide 31; LYRDTAVFECLPQHAMFG) in domain III of β2-glycoprotein I. β2GPI-reactive CD4T cells from the two models differed primarily in cytokine production: T cells from mice with induced SLE expressed IFN-γ, while T cells from MRL/lpr mice expressed both IL-17 and IFN-γ, indicating that IL-17-expressing T cells are not necessary for generating a β2GPI-reactive T cell response. These data suggest that the generation of a β2-glycoprotein I-reactive T cell response is shared by both induced and spontaneous models of systemic lupus erythematosus and that this T cell response may mediate epitope spread to autoantibodies in both models.

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