title: An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1.
abstract: Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1-infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1-infected individual with SLE who exhibited controlled viral load (<5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient's plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells.
authors.forename: Mattia
authors.initials: M
authors.lastname: Bonsignori
authors.forename: Kevin
authors.initials: K
authors.lastname: Wiehe
authors.forename: Sebastian K
authors.initials: SK
authors.lastname: Grimm
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lynch
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Kozink
authors.forename: Florence
authors.initials: F
authors.lastname: Perrin
authors.forename: Abby J
authors.initials: AJ
authors.lastname: Cooper
authors.forename: Kwan-Ki
authors.initials: KK
authors.lastname: Hwang
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Mengfei
authors.initials: M
authors.lastname: Liu
authors.forename: Krisha
authors.initials: K
authors.lastname: McKee
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Parks
authors.forename: Joshua
authors.initials: J
authors.lastname: Eudailey
authors.forename: Minyue
authors.initials: M
authors.lastname: Wang
authors.forename: Megan
authors.initials: M
authors.lastname: Clowse
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Criscione-Schreiber
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Ackerman
authors.forename: Scott D
authors.initials: SD
authors.lastname: Boyd
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Garnett
authors.initials: G
authors.lastname: Kelsoe
authors.forename: Laurent
authors.initials: L
authors.lastname: Verkoczy
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kepler
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000097:blood / Q000737:chemistry / Q000235:genetics; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D001323:Autoantibodies / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D015483:HIV Antibodies / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000150:complications* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry; D009154:Mutation; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D019562:Viral Load
chemical_list: D000974:Antibodies, Antinuclear; D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D046912:Multiprotein Complexes; C514793:gp120 protein, Human immunodeficiency virus 1; D004247:DNA