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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 (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 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 Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 12, 2004 Accepted March 14, 2004 Germline 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, Alessandro Sette, Jenni Loyall, Scott Southwood, Richard B Bankert, and Steven H Bernstein* Department of Microbiology and Immunology, Witebsky Center for Microbial Pathogenesis and Immunology, State University of New York at Buffalo, Buffalo, NY, USA La Jolla Institute of Allergy and Immunology, San Diego, CA, USA Epimmune Inc., San Diego, CA, USA James P. Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY, USA * Corresponding author; email: steven_Bernstein{at}urmc.rochester.edu. Previous studies have suggested that murine T-cells are tolerant to epitopes derived from germline variable regions of immunoglobulin (Ig) heavy (VH) or light chains. This has lead to the prediction that germline VH-region epitopes found in neoplastic B-cells cannot be utilized to provoke an anti-tumor 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 germline VH gene with specificity for dextran was generated and used as a tumor model. Using algorithms for predicting 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 germline VH peptides, when presented by dendritic cells are immunogenic in vitro and provoke a tumor-specific protective immune response in vivo. We conclude that; (a) it is possible to induce a T-cell response to germline VH peptides; (b) such peptides can be utilized to generate a B-cell tumor specific vaccine; (c) 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: S. P. Hilchey, O. Hyrien, T. R. Mosmann, A. M. Livingstone, J. W. Friedberg, F. Young, R. I. Fisher, R. J. Kelleher Jr, R. B. Bankert, and S. H. Bernstein Rituximab immunotherapy results in the induction of a lymphoma idiotype-specific T-cell response in patients with follicular lymphoma: support for a "vaccinal effect" of rituximab Blood, April 16, 2009; 113(16): 3809 - 3812. [Abstract] [Full Text] [PDF] 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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