Induction of anti-aquaporin 5 autoantibodies by molecular mimicry in mice

Abstract

Molecular mimicry is the most common mechanism that breaches self-tolerance. We previously identifiedautoantibodies to aquaporin-5 (AQP5) in the sera of patients with Sjögrens syndrome and found that the aquaporinof Prevotella melaninogenica (PmAqp), an oral commensal, is highly homologous to human AQP5. This study aimedto test whether PmAqp can induce anti-AQP5 autoantibodies via molecular mimicry. From the amino acid sequenceof PmAqp, an immunizing peptide; i.e., PmE-L, was designed, which contained both the B cell epitope E and T cellepitope. C57BL/6 and BALB/c mice were subcutaneously immunized with linear or cyclic forms of PmE-L emulsifiedin incomplete Freunds adjuvant. The concentrations of the antibodies in sera were measured using enzymelinkedimmunosorbent assays. Both linear and cyclic PmE-L induced high levels of antibodies against not only theimmunized peptides but also autoantibodies against AQP5E and antibodies against PmE, a Pm homolog of AQP5E. In C57BL/6 mice; however, the cyclic form of PmE-L was more efficient than the linear form in inducing autoantibodiesagainst AQP5E that contained a cyclic epitope. The levels of anti-PmE antibodies and anti-AQP5E autoantibodiesshowed a strong positive correlation (r = 0.95, p < 0.0005), suggesting molecular mimicry. Collectively, the miceproduced anti-AQP5E autoantibodies in response to a PmAqp-derived peptide. This model proved to be useful forstudying the mechanisms of autoantibody production by molecular mimicry.