title: Molecular characterization of five human anti-human immunodeficiency virus type 1 antibody heavy chains reveals extensive somatic mutation typical of an antigen-driven immune response.
abstract: We report the heavy chain variable region sequences from the cDNAs of five previously described monoclonal cell lines producing human antibodies specific for the human immunodeficiency virus type 1 and detail the molecular characteristics, germ-line origins, and extent of somatic mutation among these antibodies. Three of the five heavy chain variable regions derive from the VHIV gene family, but each has arisen from a different heavy chain variable region (VH) gene segment within the VHIV family. In addition, one is derived from a VHI gene segment, and one is derived from a VHV gene segment. Since four of the five antibodies arise from known germ-line VH elements, a precise determination of the extent of somatic variation is possible. The amount of variation from the closest germ-line sequence ranges from 4.5% to 14.8% among these antibodies, most of which is concentrated in the complementarity-determining regions. In general, the diversity (D) segments are long, characteristic of D-D fusions and/or extensive terminal deoxynucleotidyltransferase activity; however, definitive homologies cannot be found with the known germ-line D segments. Joining (JH) gene segment utilization appears random. The use of five different germ-line VH gene segments and extensive somatic mutation provides evidence that a polyclonal, antigen-driven immune response occurs during the natural infection with human immunodeficiency virus.
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75235.
authors.forename: J S
authors.initials: JS
authors.lastname: Andris
authors.forename: S
authors.initials: S
authors.lastname: Johnson
authors.forename: S
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: J D
authors.initials: JD
authors.lastname: Capra
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000235:genetics*; D000917:Antibody Formation / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D005803:Genes, Immunoglobulin; D015483:HIV Antibodies / Q000235:genetics*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D015345:Oligonucleotide Probes