title: Homogeneous processing and presentation of a recombined T cell epitope in inbred mice of different non-MHC genetic background.
abstract: CD4+ T cell responses are restricted by MHC class II-encoded glycoproteins which display antigen-derived peptides. Chimeric MalE proteins expressing foreign T cell epitopes represent a potent means to induce immune responses for recombinant vaccine design. Here, we studied the influence of the non-MHC genetic background and of the processing heterogeneity displayed by various APC types on the presentation of these chimeric proteins to T cells. For this purpose, the I-Ed-restricted poliovirus CD4+ T cell epitope was inserted into five different positions on the surface of MalE protein and the immunogenicity of the recombined T cell epitope was determined in different inbred mice. Immunization of several mouse strains expressing I-Ed with these chimeric proteins induced poliovirus-specific T cell response with four out of five constructs. In vitro presentation studies of the recombined epitope to specific T cells indicated that for a given chimeric protein the fine processing is conserved, whatever the non-H-2 genetic background of APC or the type of APC. Our results show that the insertion site in MalE modulates the immunogenicity of the recombined T cell epitope, but this phenomenon is only related to the MHC genetic background.
authors.affiliation: Unité de Biologie des Régulations Immunitaires, Institut Pasteur, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Lo-Man
authors.forename: P
authors.initials: P
authors.lastname: Martineau
authors.forename: M
authors.initials: M
authors.lastname: Hofnung
authors.forename: C
authors.initials: C
authors.lastname: Leclerc
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000494:pharmacology; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002213:Capsid / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D036022:Capsid Proteins; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D017955:Poliovirus / Q000276:immunology; D017452:Receptors, IgG / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D016207:Cytokines; D000939:Epitopes; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; C442540:VP1 protein, Poliovirus