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CD20 Mimicry by a mAb Rituximab‐Specific Linear Peptide: A Potential Tool for Active Immunotherapy of Autoimmune Diseases
Author(s) -
PEROSA FEDERICO,
FAVOINO ELVIRA,
CARAGNANO MARIA ANTONIETTA,
DAMMACCO FRANCO
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1361.112
Subject(s) - mimotope , biopanning , rituximab , cd20 , active immunotherapy , molecular mimicry , peptide library , antigen , monoclonal antibody , peptide vaccine , peptide , phage display , immunotherapy , biology , immunology , microbiology and biotechnology , antibody , immune system , chemistry , epitope , peptide sequence , biochemistry , gene
A bstract : An attractive, whether alternative or complementary, approach to passive immunotherapy (IT) with the anti‐CD20 mAb rituximab for the treatment of autoimmune diseases is to stimulate the host to produce an anti‐CD20 immune response by using peptides that mimic CD20 (mimotopes). The only mimotope reported to target CD20 antigen is a 43‐mer polypeptide corresponding to the exposed domain of the molecule (from amino acid 142 to 184). Owing to its length, however, it failed to efficiently induce a CD20‐specific response. A search has now been made for a smaller mimotope by biopanning a phage‐display peptide library with rituximab. A total of 10 positive phage clones expressing six distinct sequences were isolated. Their alignment produced a motif that did not match any portion of the CD20 extracellular loop, whereas the motif bearing the 12‐mer linear peptide Rp10‐L specifically reacted with rituximab and inhibited its binding to CD20. Furthermore, in BALB/c mice Rp10‐L‐induced antibodies that reacted with the CD20 + B lymphoid cell line Raji but not with the C20 − T lymphoid cell line CEM. This peptide is currently being investigated to determine the effectiveness of CD20‐based active IT for the treatment of autoimmune diseases.