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Patients with systemic lupus erythematosus (SLE) have an increased incidence of infections and antibodies to the HLA-DR4, DR1 and DR3 haplotypes have been identified. In this study, the effect of human leukocyte antigen (HLA)-DR4-restricted and HLA-DR1-restricted antibodies on Epstein-Barr virus (EBV)-specific T cell responses was investigated. We found that the increase in the expression of DR4 surface antigen (DR4SA) and the binding of anti-DR4SA antibodies to DR4SA on B lymphocytes resulted in inhibition of T cell responses to EBV antigens. In contrast, anti-DR1SA antibodies did not inhibit T cell responses to EBV-specific antigens but resulted in the loss of surface DR1SA. A recombinant EBV-specific monoclonal antibody against DR4SA, but not an anti-DR4SA antibody, inhibited T cell responses to EBV antigens. A recombinant EBV-specific IgG4 antibody against DR4SA, but not an anti-DR1SA antibody, could neutralize soluble DR4SA. Therefore, the expression of DR4SA and the binding of anti-DR4SA antibodies on B lymphocytes appear to be directly involved in the inhibition of antigen-specific T cell responses. We hypothesize that the increase in DR4SA expression may result in the accumulation of activated B cells that produce anti-DR4SA IgG4 and may therefore play a role in the pathogenesis of systemic lupus erythematosus.When Congressman Jim Costa was appointed last June to succeed Ted Lieu, he could have asked his friend and district leader Bill Edwards for help.

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