Peptide Vaccination with an Anchor-Replaced CTL Epitope Protects Against Human Papillomavirus Type 16-Induced Tumors Expressing the Wild-Type Epitope
| Autor: | Jacques Neefjes, Wybe Martin Kast, Anne Neisig, C. J. M. Melief, Michel P. M. Vierboom, J. W. Drijfhout, ter Schegget J, Mariet C.W. Feltkamp |
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| Rok vydání: | 1998 |
| Předmět: |
Cancer Research
Immunology chemical and pharmacologic phenomena Cross Reactions Major histocompatibility complex Epitope Cell Line Antigen-Antibody Reactions Epitopes Mice Antigen MHC class I Animals Humans Immunology and Allergy Cytotoxic T cell Amino Acid Sequence Papillomaviridae Pharmacology biology Chemistry Immunogenicity Histocompatibility Antigens Class I Papillomavirus Infections Vaccination Cell Transformation Viral Virology Cell biology Tumor Virus Infections CTL Peptide vaccine biology.protein Peptides T-Lymphocytes Cytotoxic |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1524-9557 |
| DOI: | 10.1097/00002371-199811000-00001 |
| Popis: | Anchor residues in cytotoxic T-lymphocyte (CTL) epitope-bearing peptides are buried deep in the major histocompatibility complex (MHC) class I antigen-presenting groove and are essential for binding to MHC class I molecules. We investigated whether anchor residue replacement affects the ability of a CTL epitope to be bound and transported by MHC class I molecules and transporter associated with antigen (TAP), respectively, and affects its functionality in vivo. Therefore, both anchor residues, at positions 5 and 9, of the H-2Db-restricted CTL epitope HPV16 E7 49-57 RAHYNIVTF were systematically exchanged for one of the 19 other naturally occurring amino acid (AA). Only replacement at anchor position 9 with residues V, I, L, or M, which are documented Db motif-anchor residues at that position, allowed binding to the MHC class I H-2Db molecule as well as transport by TAP with the same efficiency as the wild-type epitope. In B6 mice (H-2b), these anchor-modified peptide epitopes efficiently induced CTL that specifically recognized the wild-type epitope. Conversely, wild-type epitope-induced CTL recognized the V9-, I9-, L9-, and M9-replaced epitopes, respectively. In terms of tumor protection against a challenge with HPV16-transformed cells, the V9-replaced epitope was as efficient as the wild-type epitope E7 49-57. Taken together, our data demonstrate that specific CTL epitope anchor replacements are allowed with respect to MHC class I binding and TAP transport, as well as with respect to antigenicity and immunogenicity in vivo. The results presented are relevant to CTL epitope-based peptide vaccine development. |
| Databáze: | OpenAIRE |
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