The epitope recognized by rituximab

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 2 sequence patterns: one motif (CAL...

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Bibliographic Details
Published in:Blood 2006-09, Vol.108 (6), p.1975-1978
Main Authors: Binder, Mascha, Otto, Florian, Mertelsmann, Roland, Veelken, Hendrik, Trepel, Martin
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Antibodies, Monoclonal - immunology
Antibodies, Monoclonal, Murine-Derived
Antigens, CD20 - chemistry
Antigens, CD20 - genetics
Antineoplastic agents
B-Lymphocytes - immunology
Binding Sites
Biological and medical sciences
Epitopes - chemistry
Epitopes - genetics
Hematologic and hematopoietic diseases
Humans
Immunotherapy
In Vitro Techniques
Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
Medical sciences
Molecular Sequence Data
Peptide Library
Pharmacology. Drug treatments
Protein Structure, Tertiary
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - immunology
Rituximab
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Summary: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 2 sequence patterns: one motif (CALMIANSC) is related to (170)ANPS(173) within CD20, while another motif (WEWTI) may mimic the CD20 segment (182)YCYSI(185). Phages displaying either motif specifically bound rituximab. Binding to rituximab by the CD20 peptides ANPS and YCYSI was weak when used separately 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).
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2006-04-014639