Characterization of new monoclonal antibodies that discriminate between soluble and membrane CD4 and compete with human anti-CD4 autoimmune sera

Abstract In this report we present results on immunization of hu-CD4 C57Black/6J transgenic mice with HIV-1 gp120 451 complexed with its receptor protein, CD4. In addition to development of anti-gp120 antibodies, these mice also produced two anti-CD4 monoclonal antibodies, designated T6 and T9. Both these antibodies recognize soluble CD4 but not membrane associated CD4. Their corresponding epitopes map to the D3–D4 domains of CD4. These characteristics are very similar to the HIV related anti-CD4 autoimmunity found in 10–15% of HIV-1 infected people. Therefore, 208 HIV-1 positive patients were screened for anti-CD4 humoral response of which 27 were found positive (13%). Sixteen of these patients were then tested for their ability to compete with the T6 and T9 anti-CD4 monoclonal antibodies. In such experiments saturating amounts of either T6 or T9 antibodies were able to prevent 20–80% of the human serum binding to immobilized soluble CD4 in competitive ELISA tests. The T6 and T9 antibodies therefore help to define distinct CD4 epitopes associated with clinical anti-CD4 autoimmunity.