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Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1.

Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1. Research Abstract Details 

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  • Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1. Abstract Text:

    g a pieterszG A Pietersz,w liW Li,c osinskiC Osinski,v apostolopoulosV Apostolopoulos,i f mckenzieI F McKenzie,

    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/K(b) and double transgenic HLA-A*0201/K(b)xhuman MUC1 (A2 K(b)MUC1) 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 K(b)MUC1 mice by immunising with mannan-native mucin (HMFG), suggesting that tolerance to MUC1 can be overcome with mannan-HMFG.

    Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1. Publishing Authors By Initials

    ga pieterszGA Pietersz,w liW Li,c osinskiC Osinski,v apostolopoulosV Apostolopoulos,if mckenzieIF McKenzie,

    For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: base sequence: repetitive sequences, nucleic acid: tandem repeat sequences research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: base sequence: repetitive sequences, nucleic acid: tandem repeat sequences research

    PUBMED ID PMID:

    MEDLINE DATE:

    Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Vaccine

    VOLUME: 18

    Page Numbers: 2059-71

    Journal Abbreviation: Vaccine

    ISSN: 0264-410X

    DAY: 3

    MONTH: Apr

    YEAR: 2000

    Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 8406899

    Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1. Keywords Mesh Terms:

    KEYWORDS: Tandem Repeat Sequences

    MESH TERMS: immunology

    Chemical & Substance for Abstract: Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1. Information

    Substance Name: milk fat globule

    Registry Number: 0

    Grant and Affiliation Information for Definition of MHC-restricted CTL epitopes from non-variable number of tandem repeat sequence of MUC1.

    AFFILIATION: The Austin Research Institute, Studley Rd, Heidelberg, Australia. g.pietersz@ari.unimelb.edu.au

    Country: ENGLAND

    ENGLAND Research PublicationENGLAND Research Publication

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    GRANT:

    ACRONYM:

    MEDLINETA: Vaccine

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