A MURINE CYTOMEGALOVIRUS-NEUTRALIZING MONOCLONAL-ANTIBODY EXHIBITS AUTOREACTIVITY AND INDUCES TISSUE-DAMAGE IN-VIVO

The autoreactivity of murine cytomegalovirus (MCMV)-neutralizing monoc lonal antibody (mAb) AC1 was examined in vitro and in vivo. Both mAb A C1 and a human antiserum reactive with U1-small nuclear ribonucleoprot ein (U1-snRNP) stained uninfected mouse embryo fibroblasts (MEF) in a speckled nuclear pattern and reacted with 70,000 molecular weight (MW) MEF nuclear antigens by immunoblotting, suggesting that mAb AC1 cross -reacted with the 70,000 MW component of U1-snRNP. However, only mAb A C1 cross-reacted with an additional epithelial cytoplasmic autoantigen present in cultured HEp2 cells. On tissue sections from uninfected mi ce, mAb AC1 predominantly reacted with a component of central and peri pheral nervous systems, although cross-reactivity with the stratum spi nosum of the skin and the outer sheath of hair follicles was also obse rved. Immunoblotting revealed that mAb AC1 reacted with phosphorylated epitopes present on a 98,000 MW MCMV structural protein and the 200,0 00 MW mouse neurofilament protein (NFP). Treatment of uninfected mice with mAb AC1 resulted in a severe interstitial pneumonia with greatly thickened and congested alveolar septa. Severe oedema of the hypodermi s and a mild mesangial proliferative glomerulonephritis were also obse rved. These results demonstrate that a mAb reacting with a MCMV struct ural phosphoprotein which can protect mice against the dissemination o f MCMV, can also promote the development of autoimmune disease. Theref ore, the production of such cross-reactive antibodies may be an import ant mechanism in the development of autoimmunity following viral infec tion.