title: Association of VH4-59 Antibody Variable Gene Usage with Recognition of an Immunodominant Epitope on the HIV-1 Gag Protein.
abstract: The human antibody response against HIV-1 infection recognizes diverse antigenic subunits of the virion, and includes a high level of antibodies to the Gag protein. We report here the isolation and characterization of a subset of Gag-specific human monoclonal antibodies (mAbs) that were prevalent in the antibody repertoire of an HIV-infected individual. Several lineages of Gag-specifc mAbs were encoded by a single antibody heavy chain variable region, VH4-59, and a representative antibody from this group designated mAb 3E4 recognized a linear epitope on the globular head of the p17 subunit of Gag. We found no evidence that mAb 3E4 exhibited any function in laboratory studies aimed at elucidating the immunologic activity, including assays for neutralization, Ab-dependent cell-mediated virus inhibition, or enhanced T cell reactivity caused by Gag-3E4 complexes. The findings suggest this immunodominant epitope in Gag protein, which is associated with VH4-59 germline gene usage, may induce a high level of B cells that encode binding but non-functional antibodies that occupy significant repertoire space following HIV infection. The studies define an additional specific molecular mechanism in the immune distraction activity of the HIV virion.
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Valentine U
authors.initials: VU
authors.lastname: Chukwuma
authors.affiliation: Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hicar
authors.affiliation: Departments of Pediatrics, Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Nicholas
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Amanda
authors.initials: A
authors.lastname: Joyner
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, United States of America; Department of Medicine, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.affiliation: Department of Medicine, University of California Irvine, Irvine, California, United States of America.
authors.forename: Gary
authors.initials: G
authors.lastname: Landucci
authors.affiliation: Department of Medicine, University of California Irvine, Irvine, California, United States of America.
authors.forename: Donald N
authors.initials: DN
authors.lastname: Forthal
authors.affiliation: Departments of Pediatrics, Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America; Children's Healthcare of Atlanta, Atlanta, Georgia, United States of America.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Spearman
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, United States of America; Department of Pediatrics, Vanderbilt University, Nashville, Tennessee, United States of America; Vanderbilt Vaccine Center, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D015683:Gene Products, gag / Q000276:immunology*; D005803:Genes, Immunoglobulin / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D008969:Molecular Sequence Data; D009500:Neutralization Tests / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D014771:Virion / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015683:Gene Products, gag; D015483:HIV Antibodies; D016056:Immunodominant Epitopes