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Blood, 1 August 2004, Vol. 104, No. 3, pp. 752-759. Prepublished online as a Blood First Edition Paper on March 30, 2004; DOI 10.1182/blood-2004-01-0105. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-01-0105v1 104/3/752    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lou, Q. Articles by Bernstein, S. H. Search for Related Content PubMed PubMed Citation Articles by Lou, Q. Articles by Bernstein, S. H. Related Collections Immunobiology Immunotherapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Germ line tumor-associated immunoglobulin VH region peptides provoke a tumor-specific immune response without altering the response potential of normal B cells Qiang Lou, Raymond J. Kelleher, Jr, Alessandro Sette, Jenni Loyall, Scott Southwood, Richard B. Bankert, and Steven H. Bernstein From the Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, State University of New York at Buffalo, Buffalo, NY; LaJolla Institute of Allergy and Immunology, San Diego, CA; Epimmune Inc, San Diego, CA; James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY. Previous studies have suggested that murine T cells are tolerant to epitopes derived from germ line variable regions of immunoglobulin (Ig) heavy (VH) or light chains. This has lead to the prediction that germ line VH-region epitopes found in neoplastic B cells cannot be used to provoke an antitumor immune response. To test these assumptions and address the question of how such a vaccine may alter the normal B-cell response, an antibody-forming B-cell hybridoma (1H6) expressing a conserved germ line VH gene with specificity for dextran was generated and used as a tumor model. Using algorithms for predicting major histocompatibility complex (MHC) binding, potential MHC class I and II binding peptides were identified within the 1H6 VH region, synthesized, and tested for MHC binding and immunogenicity. We show that germ line VH peptides, when presented by dendritic cells, are immunogenic in vitro and provoke a tumor-specific protective immune response in vivo. We conclude that (1) it is possible to induce a T-cell response to germ line VH peptides; (2) such peptides can be used to generate a B-cell tumor-specific vaccine; and (3) a vaccine targeting VH peptides expressed by the dominant dextran-specific B-cell clonotype had no effect upon the magnitude of the normal B-cell response to dextran. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Killing malignant but not normal B cells John G. Gribben Blood 2004 104: 601. [Full Text] [PDF] This article has been cited by other articles: K. M. Zirlik, D. Zahrieh, D. Neuberg, and J. G. Gribben Cytotoxic T cells generated against heteroclitic peptides kill primary tumor cells independent of the binding affinity of the native tumor antigen peptide Blood, December 1, 2006; 108(12): 3865 - 3870. [Abstract] [Full Text] [PDF] W. Guo, D. Smith, A. Guth, K. Aviszus, and L. J. Wysocki T Cell Tolerance to Germline-Encoded Antibody Sequences in a Lupus-Prone Mouse J. Immunol., August 15, 2005; 175(4): 2184 - 2190. [Abstract] [Full Text] [PDF]

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