title: A soluble divalent class I MHC/IgG1 fusion protein activates CD8+ T cells in vivo.
abstract: CD8+ T lymphocytes recognize tumor and viral antigens bound to class I major histocompatibility complexes (MHC). Tumors and viruses may evade detection by preventing antigen presentation. The present study was designed to determine whether a soluble divalent fusion protein, containing the extracellular domains of a class I MHC molecule fused to beta2-microglobulin and the constant domains of IgG1, could induce an immune response in vivo. Administration to mice of the fusion protein loaded with a tumor peptide induced peptide-specific T cell activation and retarded tumor growth. Administration of the fusion protein loaded with a glycoprotein B (gB) peptide derived from herpes simplex virus type 1 (HSV-1) induced gB-specific cytotoxic T lymphocytes and protected mice from a lethal HSV-1 challenge. These data suggest that antigen-loaded MHC/IgG fusion proteins may enhance T cell immunity in conditions where antigen presentation is altered.
authors.affiliation: William S. Rowe Division of Rheumatology, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Brenna
authors.initials: B
authors.lastname: Carey
authors.forename: Monica
authors.initials: M
authors.lastname: DeLay
authors.forename: Jane E
authors.initials: JE
authors.lastname: Strasser
authors.forename: Claudia
authors.initials: C
authors.lastname: Chalk
authors.forename: Kristen
authors.initials: K
authors.lastname: Dudley-McClain
authors.forename: Gregg N
authors.initials: GN
authors.lastname: Milligan
authors.forename: Hermine I
authors.initials: HI
authors.lastname: Brunner
authors.forename: Sherry
authors.initials: S
authors.lastname: Thornton
authors.forename: Raphael
authors.initials: R
authors.lastname: Hirsch
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006561:Herpes Simplex / Q000276:immunology / Q000401:mortality; D018259:Herpesvirus 1, Human / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins