Characterization of new monoclonal antibodies that discriminate between soluble and membrane CD4 and compete with human anti-CD4 autoimmune sera.
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.
Denisova
Galina
G
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. denisovag@post.tau.ac.il
Lideman
Ludmila
L
Spectorman
Evgenia
E
Abulafia-Lapid
Rivka
R
Burke
Michael
M
Yust
Israel
I
Gershoni
Jonathan M
JM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D015704:CD4 Antigens / Q000145:classification / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015704:CD4 Antigens; D015699:HIV Envelope Protein gp120