Identification of HIV protein-derived cytotoxic T lymphocyte (CTL) epitopes for their possible use as synthetic vaccine

Details

Serval ID
serval:BIB_F35047B86D21
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of HIV protein-derived cytotoxic T lymphocyte (CTL) epitopes for their possible use as synthetic vaccine
Journal
Clinical and Experimental Immunology
Author(s)
Brander  C., Pichler  W. J., Corradin  G.
ISSN
0009-9104 (Print)
Publication state
Published
Issued date
07/1995
Volume
101
Number
1
Pages
107-13
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul
Abstract
CTL are by far the most important defence mechanisms against viral infections, and many attempts have been undertaken to induce protective CTL in vivo. In order to identify CTL epitopes for their possible use as peptide-vaccine candidates, HIV proteins were screened for peptide sequences which (i) fulfil the binding motif of the HLA-A2.1 molecule, and (ii) are involved in the natural immune response to HIV. From 73 nonameric peptides satisfying the binding motif, 20 peptides were synthesized and their binding to HLA-A2.1 was monitored by measuring the expression of HLA-A2.1 molecules on the cell surface of the mutant cell line T2. To evaluate the involvement in natural HIV infection, strongly binding peptides were used in cytotoxicity assays to assess their capacity to generate a peptide-specific CTL response in vitro. From 20 nonameric peptides synthesized, only five showed strong binding to HLA-A2.1. All five binding peptides had the secondary anchor residues, recently proposed by Ruppert et al. [1] to be required for binding to HLA-A2.1. The discrimination between bound and unbound peptides confirmed the importance of these secondary anchor residues which, beside the known binding motif, may dictate if a peptide can bind to HLA-A2.1 or not. In HIV- donors, no CTL activity against any of the HIV-derived peptides was detectable after a 12-day in vitro stimulation. In contrast, HIV-infected persons showed a cytotoxic response against peptide-labelled target cells, suggesting that they had developed upon HIV infection a cytotoxic immune response against the identified CTL epitopes.
Keywords
Amino Acid Sequence Cell Line Epitope Mapping/*standards HIV Antigens/*immunology/*metabolism HLA-A2 Antigen/genetics/*metabolism Humans Molecular Sequence Data Protein Binding/physiology T-Lymphocytes, Cytotoxic/*immunology Vaccines, Synthetic/biosynthesis
Pubmed
Web of science
Create date
24/01/2008 14:55
Last modification date
20/08/2019 16:20
Usage data