Human Antibodies that Recognize Novel Immunodominant Quaternary Epitopes on the HIV-1 Env Protein
Publication Date
July 13, 2016
Journal
PLOS ONE
Authors
Mark D. Hicar, Xuemin Chen, Chidananda Sulli, Trevor Barnes, et al
Volume
11
Issue
7
Pages
e0158861
DOI
https://dx.plos.org/10.1371/journal.pone.0158861
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0158861
Scopus
84978698366
Mendeley
http://www.mendeley.com/research/human-antibodies-recognize-novel-immunodominant-quaternary-epitopes-hiv1-env-protein
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Mendeley | Further Information

{"title"=>"Human antibodies that recognize novel immunodominant quaternary epitopes on the HIV-1 Env protein", "type"=>"journal", "authors"=>[{"first_name"=>"Mark D.", "last_name"=>"Hicar", "scopus_author_id"=>"6507745235"}, {"first_name"=>"Xuemin", "last_name"=>"Chen", "scopus_author_id"=>"35070934300"}, {"first_name"=>"Chidananda", "last_name"=>"Sulli", "scopus_author_id"=>"7801371705"}, {"first_name"=>"Trevor", "last_name"=>"Barnes", "scopus_author_id"=>"7202510934"}, {"first_name"=>"Jason", "last_name"=>"Goodman", "scopus_author_id"=>"56661711400"}, {"first_name"=>"Hakimuddin", "last_name"=>"Sojar", "scopus_author_id"=>"7003787731"}, {"first_name"=>"Bryan", "last_name"=>"Briney", "scopus_author_id"=>"36242903800"}, {"first_name"=>"Jordan", "last_name"=>"Willis", "scopus_author_id"=>"53868443300"}, {"first_name"=>"Valentine U.", "last_name"=>"Chukwuma", "scopus_author_id"=>"56857456500"}, {"first_name"=>"Spyros A.", "last_name"=>"Kalams", "scopus_author_id"=>"7004215696"}, {"first_name"=>"Benjamin J.", "last_name"=>"Doranz", "scopus_author_id"=>"6603437820"}, {"first_name"=>"Paul", "last_name"=>"Spearman", "scopus_author_id"=>"7003742380"}, {"first_name"=>"James E.", "last_name"=>"Crowe", "scopus_author_id"=>"26642993000"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84978698366", "doi"=>"10.1371/journal.pone.0158861", "issn"=>"19326203", "pui"=>"611245427", "scopus"=>"2-s2.0-84978698366"}, "id"=>"a1c8a73b-5743-3567-bc3e-54ecb21b3d5d", "abstract"=>"© 2016 Hicar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Numerous broadly neutralizing antibodies (Abs) target epitopes that are formed or enhanced during mature HIV envelope formation (i.e. quaternary epitopes). Generally, it is thought that Env epitopes that induce broadly neutralizing Abs are difficult to access and poorly immunogenic because of the characteristic oligomerization, conformational flexibility, sequence diversity and extensive glycosylation of Env protein. To enhance for isolation of quaternary epitope-targeting Abs (QtAbs), we previously used HIV virus-like particles (VLPs) to bind B cells from long-term non-progressor subjects to identify a panel of monoclonal Abs. When expressed as recombinant full-length Abs, a subset of these novel Abs exhibited the binding profiles of QtAbs, as they either failed to bind to monomeric Env protein or showed much higher affinity for Env trimers and VLPs. These QtAbs represented a significant proportion of the B-cell response identified with VLPs. The Ab genes of these clones were highly mutated, but they did not neutralize common HIV strains. We sought to further define the epitopes targeted by these QtAbs. Competition-binding and mapping studies revealed these Abs targeted four separate epitopes; they also failed to compete for binding by Abs to known major neutralizing epitopes. Detailed epitope mapping studies revealed that two of the four epitopes were located in the gp41 subunit of Env. These QtAbs bound pre-fusion forms of antigen and showed differential binding kinetics depending on whether oligomers were produced as recombinant gp140 trimers or as full-length Env incorporated into VLPs. Antigenic regions within gp41 present unexpectedly diverse structural epitopes, including these QtAb epitopes, which may be targeted by the naturally occurring Ab response to HIV infection.", "link"=>"http://www.mendeley.com/research/human-antibodies-recognize-novel-immunodominant-quaternary-epitopes-hiv1-env-protein", "reader_count"=>10, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>5, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>5, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>3, "Chemical Engineering"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>3}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}, "Chemical Engineering"=>{"Chemical Engineering"=>1}}, "group_count"=>0}

Scopus | Further Information

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