Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice
Details
Serval ID
serval:BIB_D50578F8511D
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Assessment of immunogenicity of human Melan-A peptide analogues in HLA-A*0201/Kb transgenic mice
Journal
Journal of Immunology
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
03/1999
Volume
162
Number
6
Pages
3566-73
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Mar 15
Research Support, Non-U.S. Gov't --- Old month value: Mar 15
Abstract
Previous studies have shown that substitution of single amino acid residues in human Melan-A immunodominant peptides Melan-A27-35 and Melan-A26-35 greatly improved their binding and the stability of peptide/HLA-A*0201 complexes. In particular, one Melan-A peptide analogue was more efficient in the generation of Melan-A peptide-specific and melanoma-reactive CTL than its parental peptide in vitro from human PBL. In this study, we analyzed the in vivo immunogenicity of Melan-A natural peptides and their analogues in HLA-A*0201/Kb transgenic mice. We found that two human Melan-A natural peptides, Melan-A26-35 and Melan-A27-35, were relatively weak immunogens, whereas several Melan-A peptide analogues were potent immunogens for in vivo CTL priming. In addition, induced Melan-A peptide-specific mouse CTL cross-recognized natural Melan-A peptides and their analogues. More interestingly, these mouse CTL were also able to lyse human melanoma cell lines in vitro in a HLA-A*0201-restricted, Melan-A-specific manner. Our results indicate that the HLA-A*0201/Kb transgenic mouse is a useful animal model to perform preclinical testing of potential cancer vaccines, and that Melan-A peptide analogues are attractive candidates for melanoma immunotherapy.
Keywords
Alleles
Animals
Antigens, Neoplasm
Arginine
Cell Line
Cytotoxicity, Immunologic/genetics
Epitopes, T-Lymphocyte/immunology
H-2 Antigens/*genetics
HLA-A Antigens/*genetics
Humans
Injections, Subcutaneous
Leucine
Lymphocyte Activation/genetics
Melanoma/immunology/metabolism
Mice
Mice, Transgenic
Neoplasm Proteins/administration & dosage/*immunology/metabolism
Oligopeptides/administration & dosage/*immunology/metabolism
T-Lymphocytes, Cytotoxic/immunology/metabolism
T-Lymphocytes, Helper-Inducer/immunology
Tumor Cells, Cultured
Pubmed
Web of science
Create date
28/01/2008 12:14
Last modification date
20/08/2019 16:54