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T cells recognize PD(N/T)R motif common in a variable number of tandem repeat and degenerate repeat sequences of MUC1.

T cells recognize PD(N/T)R motif common in a variable number of tandem repeat and degenerate repeat sequences of MUC1. Research Abstract Details 

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  • T cells recognize PD(N/T)R motif common in a variable number of tandem repeat and degenerate repeat sequences of MUC1. Abstract Text:

    vladimir m pisarevVladimir M Pisarev,leo kinarskyLeo Kinarsky,thomas caffreyThomas Caffrey,franz-george hanischFranz-George Hanisch,sam sandersonSam Sanderson,michael a hollingsworthMichael A Hollingsworth,simon shermanSimon Sherman,

    The tumor-associated antigen MUC1 is a transmembrane glycoprotein, which is overexpressed in human carcinomas. Peptide epitopes, containing the PDTR fragment from the variable number of tandem repeat (VNTR) domains of MUC1 have been found to be immunodominant in T-cell and B-cell responses. However, little is known about the immunogenicity and specificity of T-cell epitopes from other regions of MUC1 that may also participate in immune responses against tumors. In this study, the combination of immunoinformatics, molecular modeling and a vaccine adjuvant strategy were used to predict and describe a novel T-cell epitope, SAPDNRPAL, located within the degenerate tandem repeat of MUC1. This peptide possesses structural similarity to both VNTR-derived SAPDTRPAP and Sendai virus peptide FAPGNYPAL, which are known to induce cytotoxic T lymphocytes (CTL). We found that SAPDNRPAL had a higher affinity for mouse H-D(b), H-2K(b) and human HLA-A2 molecules than SAPDTRPAP. A chimeric peptide (CP) containing SAPDNRPAL and an adjuvant C5a-derived decapeptide induced epitope-specific type 1 T cells in human MUC1 transgenic mice (ELISPOT). Mice that received dendritic cells (DC) pulsed with the CP or a 25-mer peptide containing the SAPDNRPAL sequence showed increased frequencies of SAPDNRPAL- and SAPDTRPAP-specific interferon-gamma producing T cells. PDTR-specific antibody 214D4 reacted with both SAPDNRPAL and SAPDTRPAP (ELISA). Altogether, our data suggest that the degenerate MUC1 repeat sequence contains the immunogenic T-cell epitope SAPDNRPAL, which is cross-reactive with the VNTR-derived peptide SAPDTRPAP. We suggest that the use of immunogenic PDNR-containing epitope(s) in vaccine strategies could be beneficial for developing increased, PD(N/T)R motif-specific T-cell responses against tumors expressing MUC1.

    T cells recognize PD(N/T)R motif common in a variable number of tandem repeat and degenerate repeat sequences of MUC1. Publishing Authors By Initials

    vm pisarevVM Pisarev,l kinarskyL Kinarsky,t caffreyT Caffrey,fg hanischFG Hanisch,s sandersonS Sanderson,ma hollingsworthMA Hollingsworth,s shermanS Sherman,

    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:

    T cells recognize PD(N/T)R motif common in a variable number of tandem repeat and degenerate repeat sequences of MUC1. Journal Published:

    PUBLICATION TYPE: Research Support, U.S. Gov't,

    Journal: International immunopharmacology

    VOLUME: 5

    Page Numbers: 315-30

    Journal Abbreviation: Int. Immunopharmacol.

    ISSN: 1567-5769

    DAY: 1

    MONTH: Feb

    YEAR: 2005

    T cells recognize PD(N/T)R motif common in a variable number of tandem repeat and degenerate repeat sequences of MUC1. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 100965259

    T cells recognize PD(N/T)R motif common in a variable number of tandem repeat and degenerate repeat sequences of MUC1. Keywords Mesh Terms:

    KEYWORDS: Tandem Repeat Sequences

    MESH TERMS: immunology

    Chemical & Substance for Abstract: T cells recognize PD(N/T)R motif common in a variable number of tandem repeat and degenerate repeat sequences of MUC1. Information

    Substance Name: Peptide Fragments

    Registry Number: 0

    Grant and Affiliation Information for T cells recognize PD(N/T)R motif common in a variable number of tandem repeat and degenerate repeat sequences of MUC1.

    AFFILIATION: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 986805 Nebraska Medical Center, Omaha, NE 68198-6805, USA.

    Country: Netherlands

    Netherlands Research PublicationNetherlands Research Publication

    AGENCY: United States NCI

    GRANT: 5R01CA84106

    ACRONYM: CA

    MEDLINETA: Int Immunopharmacol

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

    Number Hits: 0

    T cells recognize PDN/TR motif common in a variable number of tandem repeat and degenerate repeat sequences of MUC1 Related Publications

     

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