Identification of T. gondii epitopes,adjuvants, and host genetic factors that influence protection of mice and humans |
| |
| Authors: | Tze Guan Tan Ernest Mui Hua Cong William H Witola Alexandre Montpetit Stephen P Muench John Sidney Jeff Alexander Alessandro Sette Michael E Grigg Ajesh Maewal Rima McLeod |
| |
| Institution: | 1. Department of Surgery, Committees on Immunology, Molecular Medicine, and Genetics, Institute of Genomics and Systems Biology, and The College, The University of Chicago, Chicago, IL 60637, USA;2. Department of Pediatrics (Infectious Disease), Committees on Immunology, Molecular Medicine, and Genetics, Institute of Genomics and Systems Biology, and The College, The University of Chicago, Chicago, IL 60637, USA;3. Department of Parasitology, School of Medicine, Shandong University, Jinan, Shandong 250012, China;4. Centre d’Innovation, Génome Québec, Montréal, Québec H3A 1A4, Canada;5. Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, LS2 9JT, United Kingdom;6. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA;g Pharmexa-Epimmune, San Diego, CA 92121, USA;h Laboratory of Parasitic Diseases, NIAID, National Institutes of Health, Bethesda, MD 20892, USA;i Synthetic Biomolecules, San Diego, CA 92121, USA |
| |
| Abstract: | Toxoplasma gondii is an intracellular parasite that causes severe neurologic and ocular disease in immune-compromised and congenitally infected individuals. There is no vaccine protective against human toxoplasmosis. Herein, immunization of Ld mice with HF10 (HPGSVNEFDF) with palmitic acid moieties or a monophosphoryl lipid A derivative elicited potent IFN-γ production from Ld-restricted CD8+ T cells in vitro and protected mice. CD8+ T cell peptide epitopes from T. gondii dense granule proteins GRA 3, 6, 7, and Sag 1, immunogenic in humans for HLA-A02+, HLA-A03+, and HLA-B07+ cells were identified. Since peptide repertoire presented by MHC class I molecules to CD8+ T cells is shaped by endoplasmic reticulum-associated aminopeptidase (ERAAP), polymorphisms in the human ERAAP gene ERAP1 were studied and associate with susceptibility to human congenital toxoplasmosis (p < 0.05). These results have important implications for vaccine development. |
| |
| Keywords: | Toxoplasma gondii Vaccine HLA Class 1 bound peptides |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
