CHARACTERIZATION OF THE CDNA OF A BROADLY REACTIVE NEUTRALIZING HUMAN ANTI-GP 120 MONOCLONAL-ANTIBODY

The F105 mAb, identified in an HIV-1-infected individual, binds to a discontinuous epitope on the HIV-1 gp120 envelope glycoprotein, blocks the binding of gp120 to the CD4 viral receptor, and neutralizes a broad range of HIV-1 isolates. This study reports the primary nucleotide and deduced amino acid sequences of the rearranged heavy and light chains of the mAb F105. This IgG1k mAb uses a V(H) gene member of the V(H)4 gene family (V714) and is productively rearranged with a D-D fusion product of the dlr4 and da4 germline D(H) genes and the J(H5) gene. This rearranged heavy chain gene expresses the V(H)4-HV2a idiotope, which is seen in human monoclonal IgM cold agglutinins. The F105 V(k) appears to be derived from the Humvk325 germline gene and is rearranged with a J(k2) gene. For both chains, the mutational pattern in the rearranged V(H) and V(L) genes is indicative of an antigen-driven process. These studies show that production of a broadly neutralizing anti-HIV-1 antibody that recognizes determinants within the CD4 recognition site of the envelope glycoprotein is achieved by rearrangement of the V71-4 and Humvk325 germline variable region genes along with selected individual point mutations in the rearranged genes.