The role of VH determinants in systemic lupus erythematosus

The V-regions of anti-DNA antibodies contain determinants which can drive the autoimmune in SLE. Most of the evidence comes from murine studies where VH-derived epitopes accelerate the disease process in lupus prone-mice and can elicit mild inflammatory changes reminiscent of lupus in healthy animals. T helper cells reactive with VH peptides arise spontaneously during the disease and are thought to assist production of both anti-peptide antibodies and the generation of autoantibodies that deposit in the glomeruli. In mice stimulatory epitopes may be unique to autoantibodies. As tolerogens VH peptides may delay or diminish the autoimmune response by altering the production of cytokines. An artificial VH peptide, (pCONCENSUS) has been derived and this inhibits responses to VH and other autoantigens but leaves the murine immune system intact and able to generate reponses to external antigens. Limited number of studies of V-region determinants of human anti-DNA MAbs indicate prior sensitization of lupus T cells to VH determinants and that V-region reactive T cells are not deleted in periphery of healthy individuals.