Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1
Identifieur interne : 000400 ( Istex/Curation ); précédent : 000399; suivant : 000401Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1
Auteurs : Geoffrey A. Pietersz [Australie] ; Wenjun Li [Australie] ; Carla Osinski [Australie] ; Vasso Apostolopoulos [Australie] ; Ian F. C Mckenzie [Australie]Source :
- Vaccine [ 0264-410X ] ; 2000.
English descriptors
- Teeft :
- Algorithm, Amino acids, Apostolopoulos, Assay, Avsmtssvl, Breast cancer, Cancer immunol immunother, Cell epitope, Cell epitopes, Cellular immunity, Ctlp, Ctlp frequencies, Ctlp frequency, Cytotoxic, Epitope, Extracellular, Extracellular peptides, Extracellular region, Fusion protein, Hmfg, Human muc1, Immune, Immune response, Immune responses, Immunisation, Immunised, Immunised mice, Immunising, Immunogenic, Immunol, Immunother, Intracellular, Intracellular peptides, Kbmuc1, Kbmuc1 mice, Lysis, Mannan, Mice immunised, Mouse, Muc1, Muc1 vntr, Mucin, Peptide, Pietersz, Synthetic peptides, Target cells, Transgenic, Transgenic mice, Tumour, Vaccine, Various peptides, Vntr, Vntr peptide, Vntr peptides, Vntr region, Whole hmfg.
Abstract
Abstract: Mucin1 (MUC1) is expressed ubiquitously on breast cancer cells and is a potential target for the generation of cytotoxic T cells for vaccination against breast cancer. Thus far studies of the immunogenicity of MUC1 have used peptides from the variable number of tandem repeat (VNTR); mice so immunised can generate strong cellular and antibody responses to the VNTR of human MUC1. We now demonstrate that significant CTL and CTLp can be induced to other regions of MUC1. Using the whole native MUC1 molecule, the human milk fat globule membrane antigen (HMFG) linked to mannan, cytotoxic T cell precursors (CTLp) can be generated in BALB/c, C57BL/6, transgenic HLA-A*0201/Kb and double transgenic HLA-A*0201/Kb×human MUC1 (A2 KbMUC1) mice. By immunising with HMFG and testing selectively on (a) extracellular (non-VNTR); (b) VNTR and (c) intracellular peptides, it was shown that all three regions generated effective CTL. Further, the CTL responses to non-VNTR peptides were as strong as those generated to the VNTR. Epitope prediction algorithms were not particularly helpful to describe CTL epitopes: overlapping peptides had to be synthesised and tested to find the epitopes. Thus, for CTL generation, the whole HMFG molecule is a powerful immunogen when linked to mannan, especially as multiple peptide epitopes for presentation by many Class I molecules are contained within the one molecule. Furthermore, Class I restricted MUC1 CTL were generated in double transgenic A2 KbMUC1 mice by immunising with mannan-native mucin (HMFG), suggesting that tolerance to MUC1 can be overcome with mannan–HMFG.
Url:
DOI: 10.1016/S0264-410X(99)00515-0
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C Mckenzie</name><affiliation wicri:level="1"><mods:affiliation>The Austin Research Institute, Studley Rd, Heidelberg, Victoria 3084, Australia</mods:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>The Austin Research Institute, Studley Rd, Heidelberg, Victoria 3084</wicri:regionArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Vaccine</title><title level="j" type="abbrev">JVAC</title><idno type="ISSN">0264-410X</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="2000">2000</date><biblScope unit="volume">18</biblScope><biblScope unit="issue">19</biblScope><biblScope unit="page" from="2059">2059</biblScope><biblScope unit="page" to="2071">2071</biblScope></imprint><idno type="ISSN">0264-410X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0264-410X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="Teeft" xml:lang="en"><term>Algorithm</term><term>Amino acids</term><term>Apostolopoulos</term><term>Assay</term><term>Avsmtssvl</term><term>Breast cancer</term><term>Cancer immunol immunother</term><term>Cell epitope</term><term>Cell epitopes</term><term>Cellular immunity</term><term>Ctlp</term><term>Ctlp frequencies</term><term>Ctlp frequency</term><term>Cytotoxic</term><term>Epitope</term><term>Extracellular</term><term>Extracellular peptides</term><term>Extracellular region</term><term>Fusion protein</term><term>Hmfg</term><term>Human muc1</term><term>Immune</term><term>Immune response</term><term>Immune responses</term><term>Immunisation</term><term>Immunised</term><term>Immunised mice</term><term>Immunising</term><term>Immunogenic</term><term>Immunol</term><term>Immunother</term><term>Intracellular</term><term>Intracellular peptides</term><term>Kbmuc1</term><term>Kbmuc1 mice</term><term>Lysis</term><term>Mannan</term><term>Mice immunised</term><term>Mouse</term><term>Muc1</term><term>Muc1 vntr</term><term>Mucin</term><term>Peptide</term><term>Pietersz</term><term>Synthetic peptides</term><term>Target cells</term><term>Transgenic</term><term>Transgenic mice</term><term>Tumour</term><term>Vaccine</term><term>Various peptides</term><term>Vntr</term><term>Vntr peptide</term><term>Vntr peptides</term><term>Vntr region</term><term>Whole hmfg</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Mucin1 (MUC1) is expressed ubiquitously on breast cancer cells and is a potential target for the generation of cytotoxic T cells for vaccination against breast cancer. Thus far studies of the immunogenicity of MUC1 have used peptides from the variable number of tandem repeat (VNTR); mice so immunised can generate strong cellular and antibody responses to the VNTR of human MUC1. We now demonstrate that significant CTL and CTLp can be induced to other regions of MUC1. Using the whole native MUC1 molecule, the human milk fat globule membrane antigen (HMFG) linked to mannan, cytotoxic T cell precursors (CTLp) can be generated in BALB/c, C57BL/6, transgenic HLA-A*0201/Kb and double transgenic HLA-A*0201/Kb×human MUC1 (A2 KbMUC1) mice. By immunising with HMFG and testing selectively on (a) extracellular (non-VNTR); (b) VNTR and (c) intracellular peptides, it was shown that all three regions generated effective CTL. Further, the CTL responses to non-VNTR peptides were as strong as those generated to the VNTR. Epitope prediction algorithms were not particularly helpful to describe CTL epitopes: overlapping peptides had to be synthesised and tested to find the epitopes. Thus, for CTL generation, the whole HMFG molecule is a powerful immunogen when linked to mannan, especially as multiple peptide epitopes for presentation by many Class I molecules are contained within the one molecule. Furthermore, Class I restricted MUC1 CTL were generated in double transgenic A2 KbMUC1 mice by immunising with mannan-native mucin (HMFG), suggesting that tolerance to MUC1 can be overcome with mannan–HMFG.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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