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    Clustering of Th cell epitopes on exposed regions of HIV envelope despite defects in antibody activity

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    Author
    Brown, SA; Stambas, J; Zhan, XY; Slobod, KS; Coleclough, C; Zirkel, A; Surman, S; White, SW; Doherty, PC; Hurwitz, JL
    Date
    2003-10-15
    Source Title
    JOURNAL OF IMMUNOLOGY
    Publisher
    AMER ASSOC IMMUNOLOGISTS
    University of Melbourne Author/s
    Stambas, John; Doherty, Peter
    Affiliation
    Microbiology And Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Brown, S. A., Stambas, J., Zhan, X. Y., Slobod, K. S., Coleclough, C., Zirkel, A., Surman, S., White, S. W., Doherty, P. C. & Hurwitz, J. L. (2003). Clustering of Th cell epitopes on exposed regions of HIV envelope despite defects in antibody activity. JOURNAL OF IMMUNOLOGY, 171 (8), pp.4140-4148. https://doi.org/10.4049/jimmunol.171.8.4140.
    Access Status
    This item is currently not available from this repository
    URI
    http://hdl.handle.net/11343/26580
    DOI
    10.4049/jimmunol.171.8.4140
    Description

    C1 - Journal Articles Refereed

    Abstract
    A long-standing question in the field of immunology concerns the factors that contribute to Th cell epitope immunodominance. For a number of viral membrane proteins, Th cell epitopes are localized to exposed protein surfaces, often overlapping with Ab binding sites. It has therefore been proposed that Abs on B cell surfaces selectively bind and protect exposed protein fragments during Ag processing, and that this interaction helps to shape the Th cell repertoire. While attractive in concept, this hypothesis has not been thoroughly tested. To test this hypothesis, we have compared Th cell peptide immunodominance in normal C57BL/6 mice with that in C57BL/6( micro MT/ micro MT) mice (lacking normal B cell activity). Animals were first vaccinated with DNA constructs expressing one of three different HIV envelope proteins, after which the CD4(+) T cell response profiles were characterized toward overlapping peptides using an IFN-gamma ELISPOT assay. We found a striking similarity between the peptide response profiles in the two mouse strains. Profiles also matched those of previous experiments in which different envelope vaccination regimens were used. Our results clearly demonstrate that normal Ab activity is not required for the establishment or maintenance of Th peptide immunodominance in the HIV envelope response. To explain the clustering of Th cell epitopes, we propose that localization of peptide on exposed envelope surfaces facilitates proteolytic activity and preferential peptide shuttling through the Ag processing pathway.
    Keywords
    Cellular Immunology; Immune System and Allergy

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