Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-12-21
pubmed:abstractText
Evidence obtained from both animal models and humans suggests that T cells specific for HSV-1 and HSV-2 glycoprotein D (gD) contribute to protective immunity against herpes infection. However, knowledge of gD-specific human T cell responses is limited to CD4+ T cell epitopes, with no CD8+ T cell epitopes identified to date. In this study, we screened the HSV-1 gD amino acid sequence for HLA-A*0201-restricted epitopes using several predictive computational algorithms and identified 10 high probability CD8+ T cell epitopes. Synthetic peptides corresponding to four of these epitopes, each nine to 10 amino acids in length, exhibited high-affinity binding in vitro to purified human HLA-A*0201 molecules. Three of these four peptide epitopes, gD53-61, gD70-78, and gD278-286, significantly stabilized HLA-A*0201 molecules on T2 cell lines and are highly conserved among and between HSV-1 and HSV-2 strains. Consistent with this, in 33 sequentially studied HLA-A*0201-positive, HSV-1-seropositive, and/or HSV-2-seropositive healthy individuals, the most frequent and robust CD8+ T cell responses, assessed by IFN-gamma ELISPOT, CD107a/b cytotoxic degranulation, and tetramer assays, were directed mainly against gD53-61, gD70-78, and gD278-286 epitopes. In addition, CD8+ T cell lines generated by gD53-61, gD70-78, and gD278-286 peptides recognized infected target cells expressing native gD. Lastly, CD8+ T cell responses specific to gD53-61, gD70-78, and gD278-286 epitopes were induced in HLA-A*0201 transgenic mice following ocular or genital infection with either HSV-1 or HSV-2. The functional gD CD8+ T cell epitopes described herein are potentially important components of clinical immunotherapeutic and immunoprophylactic herpes vaccines.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD8, http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte, http://linkedlifedata.com/resource/pubmed/chemical/HLA-A*02:01 antigen, http://linkedlifedata.com/resource/pubmed/chemical/HLA-A Antigens, http://linkedlifedata.com/resource/pubmed/chemical/HLA-A2 Antigen, http://linkedlifedata.com/resource/pubmed/chemical/Herpesvirus Vaccines, http://linkedlifedata.com/resource/pubmed/chemical/Peptides, http://linkedlifedata.com/resource/pubmed/chemical/Viral Envelope Proteins, http://linkedlifedata.com/resource/pubmed/chemical/glycoprotein D, Human herpesvirus 1, http://linkedlifedata.com/resource/pubmed/chemical/glycoprotein D-herpes simplex..., http://linkedlifedata.com/resource/pubmed/chemical/herpes simplex virus-1...
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
180
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
426-37
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
HLA-A*0201-restricted CD8+ cytotoxic T lymphocyte epitopes identified from herpes simplex virus glycoprotein D.
pubmed:affiliation
Laboratory of Cellular and Molecular Immunology, Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural