Linked Life Data

12917462

Source:http://linkedlifedata.com/resource/pubmed/id/12917462

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 9
pubmed:dateCreated
2003-8-14
pubmed:abstractText
MHC-I-restricted cytotoxic responses are considered a critical component of protective immunity against viruses, including human immunodeficiency virus type 1 (HIV-1). CTLs directed against accessory and early regulatory HIV-1 proteins might be particularly effective; however, CTL epitopes in these proteins are rarely found. Novel artificial neural networks (ANNs) were used to quantitatively predict HLA-A2-binding CTL epitope peptides from publicly available full-length HIV-1 protein sequences. Epitopes were selected based on their novelty, predicted HLA-A2-binding affinity and conservation among HIV-1 strains. HLA-A2 binding was validated experimentally and binders were tested for their ability to induce CTL and IFN-gamma responses. About 69 % were immunogenic in HLA-A2 transgenic mice and 61 % were recognized by CD8(+) T-cells from 17 HLA-A2 HIV-1-positive patients. Thus, 31 novel conserved CTL epitopes were identified in eight HIV-1 proteins, including the first HLA-A2 minimal epitopes ever reported in the accessory and regulatory proteins Vif, Vpu and Rev. Interestingly, intermediate-binding peptides of low or no immunogenicity (i.e. subdominant epitopes) were found to be antigenic and more conserved. Such epitope peptides were anchor-optimized to improve immunogenicity and further increase the number of potential vaccine epitopes. About 67 % of anchor-optimized vaccine epitopes induced immune responses against the corresponding non-immunogenic naturally occurring epitopes. This study demonstrates the potency of ANNs for identifying putative virus CTL epitopes, and the new HIV-1 CTL epitopes identified should have significant implications for HIV-1 vaccine development. As a novel vaccine approach, it is proposed to increase the coverage of HIV variants by including multiple anchor-optimized variants of the more conserved subdominant epitopes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1317
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2409-21
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12917462-Adult, pubmed-meshheading:12917462-Animals, pubmed-meshheading:12917462-CD8-Positive T-Lymphocytes, pubmed-meshheading:12917462-Epitopes, T-Lymphocyte, pubmed-meshheading:12917462-Female, pubmed-meshheading:12917462-Gene Products, rev, pubmed-meshheading:12917462-Gene Products, vif, pubmed-meshheading:12917462-HIV Infections, pubmed-meshheading:12917462-HIV-1, pubmed-meshheading:12917462-HLA-A2 Antigen, pubmed-meshheading:12917462-Human Immunodeficiency Virus Proteins, pubmed-meshheading:12917462-Humans, pubmed-meshheading:12917462-Male, pubmed-meshheading:12917462-Mice, pubmed-meshheading:12917462-Mice, Transgenic, pubmed-meshheading:12917462-Middle Aged, pubmed-meshheading:12917462-Oligopeptides, pubmed-meshheading:12917462-Species Specificity, pubmed-meshheading:12917462-T-Lymphocytes, Cytotoxic, pubmed-meshheading:12917462-Viral Regulatory and Accessory Proteins, pubmed-meshheading:12917462-rev Gene Products, Human Immunodeficiency Virus, pubmed-meshheading:12917462-vif Gene Products, Human Immunodeficiency Virus
pubmed:year
2003
pubmed:articleTitle
Optimization and immune recognition of multiple novel conserved HLA-A2, human immunodeficiency virus type 1-specific CTL epitopes.
pubmed:affiliation
Department of Virology, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen S, Denmark.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't