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 L(d) mice with HF10 (HPGSVNEFDF) with palmitic acid moieties or a monophosphoryl lipid A derivative elicited potent IFN-gamma production from L(d)-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.
Copyright 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / pharmacology*
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Aminopeptidases / genetics
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Animals
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Antigens, Protozoan / immunology*
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CD8-Positive T-Lymphocytes / immunology
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Epitopes, T-Lymphocyte / immunology*
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Female
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Genetic Predisposition to Disease
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HLA-A Antigens / immunology
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HLA-B Antigens / immunology
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Humans
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Interferon-gamma / immunology
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Leukocytes, Mononuclear / immunology
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Lipopeptides / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Minor Histocompatibility Antigens
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Models, Molecular
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Polymorphism, Genetic
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Protozoan Proteins / immunology*
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Protozoan Vaccines / immunology*
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Toxoplasma / immunology
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Toxoplasmosis / genetics*
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Toxoplasmosis / immunology
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Toxoplasmosis, Congenital / genetics
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Toxoplasmosis, Congenital / immunology
Substances
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Adjuvants, Immunologic
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Antigens, Protozoan
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Epitopes, T-Lymphocyte
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GRA3 protein, Toxoplasma gondii
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GRA6 protein, Toxoplasma gondii
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GRA7 protein, Toxoplasma gondii
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HLA-A Antigens
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HLA-B Antigens
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Lipopeptides
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Minor Histocompatibility Antigens
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Protozoan Proteins
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Protozoan Vaccines
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SAG1 antigen, Toxoplasma
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Interferon-gamma
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Aminopeptidases
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ERAP1 protein, human
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ERAP2 protein, human