MHC class II-bound self peptides from autoimmune MRL/lpr mice reveal potential T cell epitopes for autoantibody production in murine systemic lupus erythematosus

The systemic lupus erythematosus-like syndrome in MRL/lpr mice involves hig h-titered IgG autoantibodies, particularly antinuclear Abs that target hist ones, DNA, and RNA particles. Although T cell help is required for the gene ration of antinuclear Abs, the epitopes recognized by such helper T cells a re unknown. To address this question, we isolated and sequenced self peptid es bound by MHC class II molecules from MRL/lpr mice. We identified a numbe r of peptides that are not seen in similar preparations from nonautoimmune C3H animals. The "abnormal" peptide donors include histone, a protein compo nent of a small nuclear ribonucleoprotein, ribosomal proteins, and RNA proc essing enzymes. We postulate that the peptides from these donors are T cell epitopes required for the generation of the most frequent antinuclear Abs specificities seen in MRL/lpr mice,