Molecular characterization of variable heavy and light chain regions of five HIV type 1-specific human monoclonal antibodies.
We have reported the generation and characterization of four HIV-1 neutralizing human monoclonal antibodies. Three antibodies recognize a conformational epitope within the CD4-binding site of HIV-1 gp120 and one recognizes a linear epitope located within the hypervariable V3 domain of gp120. In the present study we report the nucleotide sequences of the cDNAs encoding the variable regions of the heavy and light chains of these antibodies. Molecular characteristics, closet germline genes, and the putative extent of somatic mutation are presented. Two of the four heavy chain variable (VH) regions are derived from the VH1 gene family, one from the VH3 gene family, and one from the VH5 gene family. In addition, the VH chain of a previously described human monoclonal antibody, directed against HIV-1 gp41, is derived from the VH3 gene family. The degree of nucleotide variation between these five antibodies and their closest germline counterparts ranges from 4 to 12%, mainly located in the complementarity-determining regions. Significant nucleotide sequence homology with previously described germline diversity (D) genes could be found for only two of five antibody D segments. Joining (JH) gene segments utilized are JH4 or JH6. Two light chain variable (VL) regions are derived from a VK1 gene segment, one from a V kappa 4, one from a V lambda 2, and one from a lambda 6 gene segment.
van der Donk
E M
EM
Department of Virology, Erasmus University, Rotterdam, The Netherlands.
Schutten
M
M
Osterhaus
A D
AD
van der Heijden
R W
RW
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D018076:DNA, Complementary; D015483:HIV Antibodies / Q000235:genetics* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region