Combined structural and immunological refinement of HIV-1 HLA-B8-restricted cytotoxic T lymphocyte epitopes.
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.
Goulder
P J
PJ
Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, GB.
Reid
S W
SW
Price
D A
DA
O'Callaghan
C A
CA
McMichael
A J
AJ
Phillips
R E
RE
Jones
E Y
EY
D000940:Antigenic Variation / Q000502:physiology; D018360:Crystallography, X-Ray; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry* / Q000502:physiology; D015488:HIV Antigens / Q000737:chemistry* / Q000276:immunology; D016655:HIV Core Protein p24 / Q000737:chemistry; D015795:HLA-B8 Antigen / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry* / Q000276:immunology
D000939:Epitopes; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015795:HLA-B8 Antigen; D009842:Oligopeptides