Identification of an antigenic and immunogenic motif expressed by two 7-mer rituximab-specific cyclic peptide mimotopes: implication for peptide-based active immunotherapy.
Two 7-mer cyclic peptides-Rp15-C and Rp13-C-which bear the antigenic motif recognized by the anti-CD20 mAb rituximab, but have different motif-surrounding amino acids, show a comparable avidity for rituximab and inhibit the binding of rituximab to raft-associated CD20 and rituximab-induced membrane ceramide on human lymphoid Daudi cells. Their immunogenic profiles differed: Abs recognizing CD20 were induced in two and five of five BALB/c mice immunized with Rp15-C and Rp13-C, respectively. Analysis of immunogenic motif, performed by panning a 7-mer phage-display peptide library with purified anti-peptide IgGs, showed that the motif defined by anti-Rp15-C mostly included amino acids surrounding the rituximab-specific antigenic motif <aNPS>, whereas that defined by anti-Rp13-C was <NPS>. These data indicate that their motif-surrounding amino acids can markedly influence the specificity of Abs, even when elicited with a short 7-mer peptide. Because these anti-peptide Abs are of IgG isotype, their specificity is likely to reflect how peptides are processed at the T cell level and suggest that, within a short peptide, the motifs defined by T cells during the initial phase and upon their stimulation may be different. Our findings may account for the failure of most forms of peptide-based immunotherapy in cancer and autoimmune diseases in which anti-mimotope Abs are expected to play a relevant therapeutic effect. They also suggest strategies to implement the specificity of peptide-induced Abs against the target Ag.
Perosa
Federico
F
Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. f.perosa@dimo.uniba.it
Favoino
Elvira
E
Vicenti
Chiara
C
Merchionne
Francesca
F
Dammacco
Franco
F
D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D058846:Antibodies, Monoclonal, Murine-Derived; D002460:Cell Line; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007167:Immunotherapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010456:Peptides, Cyclic / Q000276:immunology*; D000069283:Rituximab; D012680:Sensitivity and Specificity
D000906:Antibodies; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000939:Epitopes; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; D000069283:Rituximab