TY - JOUR
T1 - Characterization of new monoclonal antibodies that discriminate between soluble and membrane CD4 and compete with human anti-CD4 autoimmune sera
AU - Denisova, Galina
AU - Lideman, Ludmila
AU - Spectorman, Evgenia
AU - Abulafia-Lapid, Rivka
AU - Burke, Michael
AU - Yust, Israel
AU - Gershoni, Jonathan M.
N1 - Funding Information:
The authors thank Dr. Gerardo Lederkremer and Dr. A. Bobkov for fruitful discussion and advice. This study was supported by Israel Center for Emerging Diseases and by Israel Science Foundation.
PY - 2003/9
Y1 - 2003/9
N2 - In this report we present results on immunization of hu-CD4 C57Black/6J transgenic mice with HIV-1 gp120451 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.
AB - In this report we present results on immunization of hu-CD4 C57Black/6J transgenic mice with HIV-1 gp120451 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.
KW - AIDS
KW - Antibody
KW - Autoimmunity
KW - CD4 receptor
KW - Epitope
UR - http://www.scopus.com/inward/record.url?scp=0042427499&partnerID=8YFLogxK
U2 - 10.1016/S0161-5890(03)00147-0
DO - 10.1016/S0161-5890(03)00147-0
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AN - SCOPUS:0042427499
SN - 0161-5890
VL - 40
SP - 231
EP - 239
JO - Molecular Immunology
JF - Molecular Immunology
IS - 5
ER -