Linked Life Data

10612661

Source:http://linkedlifedata.com/resource/pubmed/id/10612661

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2000-2-1
pubmed:abstractText
The Kennedy peptide, (731)PRGPDRPEGIEEEGGERDRDRS(752), from the cytoplasmic domain of the gp41 transmembrane envelope glycoprotein of HIV-1 contains a conformationally dependent neutralizing epitope (ERDRD) and a linear nonneutralizing epitope (IEEE). No recognized murine T cell epitope is present. The peptide usually stimulates virus-specific antibody, but this is not always neutralizing. Here we show that IEEE (or possibly IEEE plus adjacent sequence) is immunogenically and antigenically dominant over the ERDRD neutralizing epitope. Thus rabbits immunized in a variety of routes, doses, and adjuvants with a chimeric cowpea mosaic virus (CPMV) expressing the Kennedy peptide on its surface (CPMV-HIV/1) synthesized IEEE-specific serum antibody but no ERDRD-specific or HIV-1-neutralizing antibody. To test if this resulted from immunodominance or from a hole in the antibody repertoire, we immunized rabbits with chimera CPMV-HIV/29, which expresses the GERDRDR part of the Kennedy sequence. This chimera readily stimulated ERDRD-specific, neutralizing antibody. In mice the situation was less extreme, but individual animals with low neutralizing titers had a high ratio of IEEE-specific:ERDRD-specific antibody. Data are consistent with immunodominance of IEEE over ERDRD in the Kennedy peptide. IEEE-specific antibody was also antigenically dominant and prevented ERDRD-specific antibody from binding to its epitope and from neutralizing HIV-1. It may be that HIV-1 has evolved a nonneutralizing immunodominant epitope that allows it to possess a neutralizing epitope without suffering the consequences, and this idea is supported by the covariance of both epitope sequences. To our knowledge this is the first example of a defined sequence that controls the activity of an adjacent epitope.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0042-6822
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Academic Press.
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
266
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
66-78
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10612661-Amino Acid Sequence, pubmed-meshheading:10612661-Animals, pubmed-meshheading:10612661-Antibodies, Monoclonal, pubmed-meshheading:10612661-Antibody Specificity, pubmed-meshheading:10612661-Comovirus, pubmed-meshheading:10612661-Gene Deletion, pubmed-meshheading:10612661-HIV Antibodies, pubmed-meshheading:10612661-HIV Antigens, pubmed-meshheading:10612661-HIV Envelope Protein gp41, pubmed-meshheading:10612661-HIV-1, pubmed-meshheading:10612661-Humans, pubmed-meshheading:10612661-Immunization, pubmed-meshheading:10612661-Immunodominant Epitopes, pubmed-meshheading:10612661-Mice, pubmed-meshheading:10612661-Mice, Inbred C3H, pubmed-meshheading:10612661-Molecular Sequence Data, pubmed-meshheading:10612661-Neutralization Tests, pubmed-meshheading:10612661-RNA Viruses, pubmed-meshheading:10612661-Rabbits, pubmed-meshheading:10612661-Recombinant Fusion Proteins
pubmed:year
2000
pubmed:articleTitle
Immunogenic and antigenic dominance of a nonneutralizing epitope over a highly conserved neutralizing epitope in the gp41 envelope glycoprotein of human immunodeficiency virus type 1: its deletion leads to a strong neutralizing response.
pubmed:affiliation
Department of Biological Sciences, University of Warwick, Coventry, CV4 7AL, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't