SEARCH:   Advanced

Blood, 15 September 2006, Vol. 108, No. 6, pp. 1975-1978. Prepublished online as a Blood First Edition Paper on May 16, 2006; DOI 10.1182/blood-2006-04-014639. This Article Full Text (PDF) All Versions of this Article: blood-2006-04-014639v1 108/6/1975    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 Binder, M. Articles by Trepel, M. Search for Related Content PubMed PubMed Citation Articles by Binder, M. Articles by Trepel, M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 3, 2006 Accepted May 2, 2006 The epitope recognized by rituximab Mascha Binder, Florian Otto, Roland Mertelsmann, Hendrik Veelken, and Martin Trepel* Department of Hematology and Oncology, University of Freiburg Medical Center Department of Hematology and Oncology, Freiburg University Medical Center * Corresponding author; email: trepel{at}mm11.ukl.uni-freiburg.de. Rituximab is a monoclonal antibody widely used in the treatment of malignant lymphoma and autoimmunity. Its epitope within the B-cell antigen CD20 is largely unknown. We used phage display libraries to select peptides binding to rituximab. Enriched peptides showed two sequence patterns: one (CALMIANSC) is related to (170)ANPS(173) within CD20 while another motif (WEWTI) may mimic the CD20 segment (182)YCYSI(185). Phage displaying either motif specifically bound rituximab. Binding to rituximab by the CD20 peptides ANPS and YCYSI was weak and enhanced when both peptides were linked. Recombinant CD20 extracellular loop proteins blocked binding of the selected CWWEWTIGC phage to rituximab suggesting that CWWEWTIGC mimics the epitope. Blocking capacity was strongly reduced upon mutation of the CD20 strings ANPS or YCYSI. We conclude that rituximab binds a discontinuous epitope in CD20, comprised of (170)ANPS(173) and (182)YCYSI(185) with both strings brought in steric proximity by a disulfide bridge between C(167) and C(183). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Small mimotopes are big in identifying B-cell epitopes Erika Jensen-Jarolim and Angelika B. Riemer Blood 2006 108: 1794-1795. [Full Text] [PDF] This article has been cited by other articles: B. Li, S. Shi, W. Qian, L. Zhao, D. Zhang, S. Hou, L. Zheng, J. Dai, J. Zhao, H. Wang, et al. Development of Novel Tetravalent Anti-CD20 Antibodies with Potent Antitumor Activity Cancer Res., April 1, 2008; 68(7): 2400 - 2408. [Abstract] [Full Text] [PDF] P. Martin, R. R. Furman, M. Coleman, and J. P. Leonard Phase I to III Trials of Anti B Cell Therapy in Non Hodgkin's Lymphoma Clin. Cancer Res., September 15, 2007; 13(18): 5636s - 5642s. [Abstract] [Full Text] [PDF] J. Du, H. Wang, C. Zhong, B. Peng, M. Zhang, B. Li, S. Huo, Y. Guo, and J. Ding Structural Basis for Recognition of CD20 by Therapeutic Antibody Rituximab J. Biol. Chem., May 18, 2007; 282(20): 15073 - 15080. [Abstract] [Full Text] [PDF] M. Binder, F.-N. Vogtle, S. Michelfelder, F. Muller, G. Illerhaus, S. Sundararajan, R. Mertelsmann, and M. Trepel Identification of Their Epitope Reveals the Structural Basis for the Mechanism of Action of the Immunosuppressive Antibodies Basiliximab and Daclizumab Cancer Res., April 15, 2007; 67(8): 3518 - 3523. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020