title: Genetic immunization maps T cell (auto)immune responses to self antigens homologous to exogenous proteins.
abstract: Genetic immunization represents a new tool for investigating physiological and pathological immune responses. Here we used genetic immunization with naked DNA to study the immune relevance of aminoacid sequence homologies by evaluating the outcome of immunization to a viral protein homologous to an HLA molecule. The viral protein was Balf2, a protein of Epstein-Barr virus (EBV) that shares aminoacid sequence homology with the HLA allele DRB1*0801. After genetic immunization of BALB/c mice with a construct encoding Balf2, we analyzed T cell responses of immunized mice. We found that cross-reactive proliferative and cytotoxic responses were raised to the homologous sequence as expressed by HLA-DRB1*0801. Furthermore, preferential secretion of Th1-type pro-inflammatory cytokines occurred. This strategy can allow rapid screening of interactive immune networks involving aminoacid sequence homologies between organisms.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093-0663, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: La Cava
authors.forename: Margherita
authors.initials: M
authors.lastname: Massa
authors.forename: Alberto
authors.initials: A
authors.lastname: Mendivil
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Albani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000737:chemistry* / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D049109:Cell Proliferation; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000276:immunology; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000276:immunology; D006684:HLA-DR Antigens / Q000737:chemistry* / Q000276:immunology; D059811:HLA-DRB1 Chains; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000276:immunology
chemical_list: D001324:Autoantigens; C096364:BALF2 protein, Human herpesvirus 4; D016207:Cytokines; D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C466440:HLA-DRB1*08:01 antigen; D014764:Viral Proteins; D004247:DNA