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

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 beta 2-glycoprotein I. Notably, mice immunized with beta 2-glycoprotein I and lipopolysaccharide develop a strong T cell response to beta 2-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 beta 2-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 beta 2GPI. We found that mice with induced and spontaneous systemic lupus erythematosus recognize a common T cell epitope (peptide 31; LYRDTAVFECLPQHAMFG) in domain III of beta 2-glycoprotein I. beta 2GPI-reactive CD4(+) T cells from the two models differed primarily in cytokine production: T cells from mice with induced SLE expressed IFN-gamma, while T cells from MRL/lpr mice expressed both IL-17 and IFN-gamma, indicating that IL-17-expressing T cells are not necessary for generating a beta 2GPI-reactive T cell response. These data suggest that the generation of a beta 2-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.