Identification of T. gondii epitopes, adjuvants, and host genetic factors that influence protection of mice and humans.

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.

• 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
• Journal: Vaccine (Vaccine) Vol. 28 Issue 23 Pg. 3977-89 (May 21 2010) ISSN: 1873-2518 [Electronic] Netherlands
• PMID: 20347630 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Adjuvants, Immunologic
• Antigens, Protozoan
• Epitopes, T-Lymphocyte
• GRA3 protein, Toxoplasma gondii
• GRA6 protein, Toxoplasma gondii
• GRA7 protein, Toxoplasma gondii
• HLA-A Antigens
• HLA-B Antigens
• Lipopeptides
• Minor Histocompatibility Antigens
• Protozoan Proteins
• Protozoan Vaccines
• SAG1 antigen, Toxoplasma
• Interferon-gamma
• Aminopeptidases
• ERAP1 protein, human
• ERAP2 protein, human

Topics

• Adjuvants, Immunologic (pharmacology)
• Aminopeptidases (genetics)
• Animals
• Antigens, Protozoan (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Female
• Genetic Predisposition to Disease
• HLA-A Antigens (immunology)
• HLA-B Antigens (immunology)
• Humans
• Interferon-gamma (immunology)
• Leukocytes, Mononuclear (immunology)
• Lipopeptides (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Transgenic
• Minor Histocompatibility Antigens
• Models, Molecular
• Polymorphism, Genetic
• Protozoan Proteins (immunology)
• Protozoan Vaccines (immunology)
• Toxoplasma (immunology)
• Toxoplasmosis (genetics, immunology)
• Toxoplasmosis, Congenital (genetics, immunology)