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: Brenna Carey, Monica DeLay, Jane E Strasser, Claudia Chalk, Kristen Dudley-McClain, Gregg N Milligan, Hermine I Brunner, Sherry Thornton, Raphael Hirsch
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 116 Issue 1 Pg. 65-76 (Jul 2005) ISSN: 1521-6616 [Print] United States
• PMID: 15925833 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Histocompatibility Antigens Class I
• Immunoglobulin G
• Peptide Fragments
• Recombinant Fusion Proteins

Topics

• Animals
• CD8-Positive T-Lymphocytes (immunology)
• Female
• Herpes Simplex (immunology, mortality)
• Herpesvirus 1, Human (immunology)
• Histocompatibility Antigens Class I (genetics, immunology)
• Immunoglobulin G (genetics, immunology)
• Lymphocyte Activation (immunology, physiology)
• Mice
• Mice, Inbred C57BL
• Neoplasms (drug therapy, immunology)
• Peptide Fragments (immunology)
• Recombinant Fusion Proteins (genetics, immunology, pharmacology)
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes, Cytotoxic (immunology)