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Combined structural and immunological refinement of HIV-1 HLA-B8-restricted cytotoxic T lymphocyte epitopes

Goulder, Philip J. R., Reid, Scott W., Price, David, O'Callaghan, Chris A., McMichael, Andrew J., Phillips, Rodney E. and Jones, E. Yvonne 1997. Combined structural and immunological refinement of HIV-1 HLA-B8-restricted cytotoxic T lymphocyte epitopes. European Journal of Immunology 27 (6) , pp. 1515-1521. 10.1002/eji.1830270630

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Abstract

This study demonstrates that use of structural information improves the definition and optimization of cytotoxic T lymphocyte (CTL) epitopes. Epitope optimization usually requires numerous truncated peptides or a reverse immunogenetic approach, where the peptide binding motif is used to predict epitopes. These binding motifs do not reliably predict all peptides which are CTL epitopes. Comparison of 24 peptides eluted from HLA-B8 with 10 HLA-B8-restricted defined CTL epitopes demonstrated that known epitopes varied considerably at anchor positions. We used structural information based on determination of the crystal structure of the HLA-B8-GGKKKYKL complex to reassess previously described CTL epitopes, to predict new epitopes, and to predict the consequences of naturally occurring variation within epitopes. These predictions were confirmed by cytotoxicity and binding assays. Use of combined structural and immunological data more accurately defines the true peptide-binding motif of a restriction element than eluted peptide data allows.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: Q Science > QR Microbiology > QR180 Immunology
Publisher: John Wiley & Sons
ISSN: 0014-2980
Date of First Compliant Deposit: 16 June 2016
Date of Acceptance: 10 April 1997
Last Modified: 04 Jun 2017 09:12
URI: http://orca.cf.ac.uk/id/eprint/91928

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