Functional and molecular characterization of human monoclonal antibody reactive with the immunodominant region of HIV type 1 glycoprotein 41.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Functional and molecular characterization of human monoclonal antibody reactive with the immunodominant region of HIV type 1 glycoprotein 41.

AIDS Res Hum Retroviruses. 1998 Sep 20;14(14):1271-80. Unique Identifier : AIDSLINE GENBANK/AF059200
Cavacini LA; Emes CL; Wisnewski AV; Power J; Lewis G; Montefiori D; Posner MR; Department of Medicine, Beth Israel Deaconess Medical Center and; Harvard Medical School, Boston, Massachusetts 02215, USA.; lcavacin@bidmc.harvard.edu

Abstract: The immunoreactivity, functional activity, and molecular features of a human monoclonal antibody (HMAb), F240, from an HIV-1-infected individual have been studied. Flow cytometric analysis demonstrated that F240 is reactive with cells infected with a broad range of laboratory isolates but not with uninfected cells. Reactivity of F240 is greatly enhanced by preincubation of infected cells with soluble CD4, and to a much lesser extent, with F105, an HMAb reactive with the CD4-binding site of gp120. This enhancement is temperature dependent, with maximum enhancement observed at 37 degrees C, and suggests that the F240 epitope may be more accessible after gp120 has bound to CD4 in vivo. Immunoblot analysis reveals antigen specificity of F240 for gp41 or its precursor gp160. F240 specificity is mapped to the immunodominant region of the gp41 ectodomain by Pepscan analysis. This epitope has been implicated in eliciting nonprotective antibodies that enhance infection in the presence of complement. Consistent with this, F240 failed to neutralize laboratory isolates and enhanced viral infection in a complement-dependent manner. The F240 VH demonstrates extensive somatic mutations compared with the product of its closest homologous germline gene VH3-3.11. Most amino acid substitutions occur in CDR2, characteristic of an antigen-driven response, and in FR3, a phenomenon observed in other anti-HIV-1 envelope HMAbs. Primary structure analysis of the F240 heavy chain revealed strong homology in the CDR domains to an HMAb (3D6) reactive with the same gp41 region, which suggests that these HMAbs could define a potential human antibody clonotype.

Keywords: JOURNAL ARTICLE Amino Acid Sequence Animal Antibodies, Monoclonal/*GENETICS/*IMMUNOLOGY Blotting, Western Cloning, Molecular Complement/IMMUNOLOGY Genes, Immunoglobulin Human HIV Envelope Protein gp120/IMMUNOLOGY HIV Envelope Protein gp41/*IMMUNOLOGY HIV Infections/*IMMUNOLOGY HIV-1/*IMMUNOLOGY *Immunodominant Epitopes Immunoglobulins, Heavy-Chain/GENETICS Immunoglobulins, Light-Chain/GENETICS Mice Molecular Sequence Data Sequence Analysis, DNA Support, U.S. Gov't, P.H.S.
990228
A9920906

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