title: Peptidomimics of antigen are present in variable region of heavy and light chains of anti-idiotypic antibody and function as surrogate antigen for perpetuation of immunological memory.
abstract: Peptide antigens composed of relevant B cell and T cell epitopes, capable of inducing protective immune response against the whole pathogen, are potentially safe, alternative vaccine antigens for prevention of wide range of diseases. Here, we show that short peptides derived from internal image sequences of anti-idiotypic antibody (peptidomimics) can function as both B and T cell epitopes and perpetuate antigen specific immunological memory. We have sequenced the variable regions of heavy and light chains of the anti-idiotypic antibody specific to rinderpest virus hemagglutinin protein and predicted T cell epitopes in these sequences by an immuno-informatics approach. We have studied the interaction of these epitopes with MHC class I by in vitro assays and in silico analysis by molecular modeling of the idiopeptide-MHC complexes as well as antigen-derived peptide-MHC complexes. The functional capacity of anti-idiotypic antibody derived peptides to stimulate antigen specific T cells in vitro was tested. The ability of peptidomimics to proliferate the immune splenocytes in vitro was 10 times more when compared with that of a control peptide taken from the constant region of immunoglobulin. Similarly three- to fivefold more amounts of IL-2 and IFN-gamma were secreted by immune splenocytes in response to in vitro re-stimulation with peptidomimics. Further, we have provided evidence for the generation of antibodies against peptidomimics in memory response generated on antigen or anti-idiotypic antibody immunizations. In summary, our experiments suggest that peptidomimics are generated in the body after antigen immunization and may have important roles in vivo in regulating antigen specific immunological memory.
authors.affiliation: Department of Microbiology and Cell biology, Indian Institute of Science, C.V. Raman Avenue, Bangalore-560 012, Karnataka, India. shaila@mcbl.iisc.ernet.in
authors.forename: J
authors.initials: J
authors.lastname: Vani
authors.forename: Jayakani
authors.initials: J
authors.lastname: Justin
authors.forename: R Chandra
authors.initials: RC
authors.lastname: Nagasuma
authors.forename: Rabindranath
authors.initials: R
authors.lastname: Nayak
authors.forename: M S
authors.initials: MS
authors.lastname: Shaila
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000737:chemistry / Q000502:physiology*; D000941:Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D018604:Epitope Mapping; D005260:Female; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000502:physiology*; D007147:Immunoglobulin Light Chains / Q000737:chemistry / Q000502:physiology*; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000502:physiology*; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D010455:Peptides