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Blood, 22 October 2009, Vol. 114, No. 17, pp. 3615-3624. Prepublished online as a Blood First Edition Paper on August 18, 2009; DOI 10.1182/blood-2009-01-197822. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2009-01-197822v1 114/17/3615    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 Google Scholar Articles by Seiler, T. Articles by Chiorazzi, N. PubMed PubMed Citation Articles by Seiler, T. Articles by Chiorazzi, N. Related Collections Immunobiology Lymphoid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Characterization of structurally defined epitopes recognized by monoclonal antibodies produced by chronic lymphocytic leukemia B cells Till Seiler1,*, Manuela Woelfle1,*, Sophia Yancopoulos1, Rosa Catera1, Wentian Li1, Katerina Hatzi1, Carol Moreno1, Marcela Torres2, Santanu Paul1, Hartmut Dohner3, Stephan Stilgenbauer3, Matthew S. Kaufman4,5, Jonathan E. Kolitz1,5,6, Steven L. Allen1,5,6, Kanti R. Rai1,4,5, Charles C. Chu1,6,7, and Nicholas Chiorazzi1,57 1 The Feinstein Institute for Medical Research, North Shore-Long Island Jewish (LIJ) Health System, Manhasset, NY; 2 Department of Microbiology, Albert Einstein College of Medicine, Bronx, NY; 3 Department of Internal Medicine III, University of Ulm, Ulm, Germany; 4 Department of Medicine, Long Island Jewish Medical Center, North Shore-LIJ Health System, New Hyde Park, NY; 5 Department of Medicine, Albert Einstein College of Medicine, Bronx, NY; 6 Department of Medicine, North Shore University Hospital, North Shore-LIJ Health System, Manhasset, NY; and 7 Department of Medicine, New York University School of Medicine, New York, NY and Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY Despite a wealth of information about the structure of surface membrane immunoglobulin (smIg) on chronic lymphocytic leukemia (CLL) cells, little is known about epitopes reacting with their binding sites. Probing phage-displayed peptide libraries, we identified and characterized mimetopes for Igs of 4 patients with IGHV mutated CLL (M-CLL) and 4 with IGHV unmutated CLL (U-CLL). Six of these mAbs were representatives of stereotyped B-cell receptors characteristic of CLL. We found that mimetic epitopes for U- and M-CLL Igs differed significantly. M-CLL–derived peptides exhibited better amino acid motifs, were more similar to each other, aligned more easily, and formed tighter clusters than U-CLL–derived peptides. Mono-, oligo-, and polyreactivity of peptides correlated with structural changes within antigen-binding sites of selecting M-CLL mAbs. Although M-CLL–isolated peptides and certain U-CLL mAbs bound more effectively to the selecting mAb, others were not as specific, reacting with M-CLL and U-CLL mAbs; these data suggest that in vivo structurally diverse epitopes could bind smIgs of distinct CLL clones, thereby altering survival and growth. Finally, an M-CLL–derived peptide inhibited, in a dose-dependent manner, binding of its homologous mAb to human B lymphocytes; therefore peptides that inhibit or alter the consequences of antigen-smIg interactions may represent therapeutic modalities in CLL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: CLL: promiscuity leads to risks Kostas Stamatopoulos Blood 2009 114: 3508-3509. [Full Text] [PDF] This article has been cited by other articles: K. Stamatopoulos CLL: promiscuity leads to risks Blood, October 22, 2009; 114(17): 3508 - 3509. [Full Text] [PDF]

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