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

Galina Denisova, Ludmila Lideman, Evgenia Spectorman, Rivka Abulafia-Lapid, Michael Burke, Israel Yust, Jonathan M. Gershoni

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)231-239
Number of pages9
JournalMolecular Immunology
Volume40
Issue number5
DOIs
StatePublished - Sep 2003

Keywords

  • AIDS
  • Antibody
  • Autoimmunity
  • CD4 receptor
  • Epitope

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