Crystal structures of two closely related but antigenically distinct HLA-A2/melanocyte-melanoma tumor-antigen peptide complexes.

Details

Serval ID
serval:BIB_E280F91F22A9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Crystal structures of two closely related but antigenically distinct HLA-A2/melanocyte-melanoma tumor-antigen peptide complexes.
Journal
Journal of immunology
Author(s)
Sliz P., Michielin O., Cerottini J.C., Luescher I., Romero P., Karplus M., Wiley D.C.
ISSN
0022-1767
Publication state
Published
Issued date
2001
Peer-reviewed
Oui
Volume
167
Number
6
Pages
3276-3284
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
We have determined high-resolution crystal structures of the complexes of HLA-A2 molecules with two modified immunodominant peptides from the melanoma tumor-associated protein Melan-A/Melanoma Ag recognized by T cells-1. The two peptides, a decamer and nonamer with overlapping sequences (ELAGIGILTV and ALGIGILTV), are modified in the second residue to increase their affinity for HLA-A2. The modified decamer is more immunogenic than the natural peptide and a candidate for peptide-based melanoma immunotherapy. The crystal structures at 1.8 and 2.15 A resolution define the differences in binding modes of the modified peptides, including different clusters of water molecules that appear to stabilize the peptide-HLA interaction. The structures suggest both how the wild-type peptides would bind and how three categories of cytotoxic T lymphocytes with differing fine specificity might recognize the two peptides.
Keywords
Amino Acid Sequence, Antigens, Neoplasm/chemistry, Antigens, Neoplasm/metabolism, Binding Sites, Crystallography, X-Ray, HLA-A2 Antigen/chemistry, HLA-A2 Antigen/metabolism, Humans, Macromolecular Substances, Melanoma/immunology, Models, Molecular, Neoplasm Proteins/chemistry, Neoplasm Proteins/metabolism, Peptide Fragments/chemistry, Peptide Fragments/metabolism, Pliability, Protein Binding, Protein Conformation, T-Lymphocytes, Cytotoxic/immunology, Water
Pubmed
Web of science
Create date
28/01/2008 11:19
Last modification date
20/08/2019 16:06
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