Lecerf, M., Scheel, T., Pashov, A.D. et al. (8 more authors) (2015) Prevalence and Gene Characteristics of Antibodies with Cofactor-induced HIV-1 Specificity. Journal of Biological Chemistry, 290 (8). 5203 - 5213. ISSN 0021-9258
Abstract
The healthy immune repertoire contains a fraction of antibodies that bind to various biologically relevant cofactors, including heme. Interaction of heme with some antibodies results in induction of new antigen binding specificities and acquisition of binding polyreactivity. In vivo, extracellular heme is released as a result of hemolysis or tissue damage; hence the post-translational acquisition of novel antigen specificities might play an important role in the diversification of the immunoglobulin repertoire and host defense. Here, we demonstrate that seronegative immune repertoires contain antibodies that gain reactivity to HIV-1 gp120 upon exposure to heme. Furthermore, a panel of human recombinant antibodies was cloned from different B cell subpopulations, and the prevalence of antibodies with cofactor-induced specificity for gp120 was determined. Our data reveal that upon exposure to heme, ∼24% of antibodies acquired binding specificity for divergent strains of HIV-1 gp120. Sequence analyses reveal that heme-sensitive antibodies do not differ in their repertoire of variable region genes and in most of the molecular features of their antigen-binding sites from antibodies that do not change their antigen binding specificity. However, antibodies with cofactor-induced gp120 specificity possess significantly lower numbers of somatic mutations in their variable region genes. This study contributes to the understanding of the significance of cofactor-binding antibodies in immunoglobulin repertoires and of the influence that the tissue microenvironment might have in shaping adaptive immune responses.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 by The American Society for Biochemistry and Molecular Biology, Inc. |
Keywords: | Antibody; Cloning; Heme; Human Immunodeficiency Virus (HIV); Immunoglobulin G (IgG); gp120; Cofactors |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 18 Jun 2015 15:24 |
Last Modified: | 08 Aug 2015 23:28 |
Published Version: | http://dx.doi.org/10.1074/jbc.M114.618124 |
Status: | Published |
Publisher: | American Society for Biochemistry and Molecular Biology |
Refereed: | Yes |
Identification Number: | 10.1074/jbc.M114.618124 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:85387 |